A Phase 1/2 interventional study of nab-paclitaxel and nab-paclitaxel in Neuroblastoma, Rhabdomyosarcoma and Ewing's Sarcoma, sponsored by Celgene. Completed at 20 sites in 7 countries. Open to participants aged 6 Months to 24 Years. Per ClinicalTrials.gov, last updated 2019-12-27.
Sponsored by Celgene (part of Bristol-Myers Squibb) · Phase 1/2, Interventional, and Treatment
The purpose of this study is to find the safe dose of nab-paclitaxel in children with solid tumors, and to see if it works to treat these solid tumors in children and young adults (in Phase 1 ≤ 18 years old and in Phase 2 ≤ 24 years old). After the final dose has been chosen, patients will be enrolled according to the specific solid tumor type, (neuroblastoma, rhabdomyosarcoma, or Ewing's sarcoma), to see how nab-paclitaxel works in treating these tumors.
ABI-007-PST-001 is a Phase 1/2, multicenter, open-label, dose-finding study to assess the safety , tolerability, and preliminary efficacy of weekly nab-paclitaxel in pediatric patients with recurrent or refractory solid tumors (excluding brain tumors). The Phase 1 portion of the study, with a dose escalation design, ended and the recommended Phase 2 dose (RP2D) was determined as 240 mg/m\^2 intravenously (IV) in patients weighing > 10 kg and 11.5 mg/kg in patients weighing ≤ 10 kg, on Days 1, 8 and 15 of a 28-day cycle. The Phase 2 portion of the study will enroll additional patients at the RP2D into 1 of 3 solid tumor groups [neuroblastomas, rhabdomyosarcomas, Ewing's sarcomas]. Both phases of the study are open-label and conducted at multiple centers.
The Phase 2 is using a Simon 2-stage design to monitor patient enrollment for each group separately. The rhabdomyosarcoma group, neuroblastoma or Ewing's sarcoma groups did not reach the expected number of 2 responders out of 14 efficacy eligible patients. Consequently, the groups were stopped.
675 studies on the registry are indexed under Neuroblastoma; 127 are open to participants now.
This study's enrollment of 107 is above the median of 32 across 507 interventional studies indexed under Neuroblastoma.
Browse Neuroblastoma studies →Celgene is the lead sponsor of 428 studies on the registry; 12 are open to participants now.
Of its 104 completed or terminated interventional studies of FDA-regulated products, 30 (29%) have results posted.
First submitted before Celgene became part of Bristol-Myers Squibb.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Patients must meet all of the following criteria to be enrolled in the study:
Patient has a confirmed solid tumor diagnosis according to the
following:
Phase 1: patient has a recurrent or solid tumor that has
progressed or did not respond to standard therapy, or for which no
standard anticancer therapy exists
The patient has adequate serum chemistry levels, evidenced by the
following laboratory values
(AST)/serum glutamic-oxaloacetric
transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic
pyruvate transaminase (SGPT) ≤ 2.5 × (ULN)
The patient has adequate bone marrow function, evidenced by the
following:
≥ 80 × 10\^9 cells/L (transfusion independent, defined as not
receiving platelet transfusions within 7 days prior to laboratory sample). In the phase 2 portion, for patients with known bone marrow involvement, platelets ≥ 50 × 10\^9 cells/L
The patient (when applicable) or patient's parent(s) or legal guardian(s)
understand(s) and voluntarily signed an document prior
to any study-related assessments/procedures being conducted. Where
locally applicable, the patient also understands and voluntarily provides
his/her assent prior to any study-related assessments/procedures being
conducted.
Male patients of must use a condom during
sexual intercourse and shall not father a child during the study and for 6 months after the last dose of study medication.
Female patients of childbearing potential [defined as all female
patients ≥ 12 years old or who have reached menarche, whichever occurs
first] must have both of the following:
a. Agree to the use of two physician-approved methods
simultaneously or practice complete abstinence while on study medication or for a longer period if required by regulations.
i. True abstinence: When this is in line with the preferred and usual
lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, postovulation methods) and withdrawal are not
acceptable methods of contraception.
ii. Acceptable contraceptive methods include: oral, injectable, or
implantable hormonal contraceptive; tubal ligation; intra-uterine device;
barrier contraceptive with spermicide; or vasectomized partner) including
at least one barrier method.
b. Have negative serum pregnancy test result at screening confirmed by
negative urine pregnancy dipstick within 72 hours prior to first dose of
product (if serum test occurred > 72 hours from first
dose); pregnancy test with sensitivity of at least 25 mIU/mL.
Exclusion Criteria:
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Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Karnofsky performance status (KPS)
A 0–100 scale of how well someone can carry out everyday activities. 100 is no complaints and no signs of illness; 70 is able to look after yourself but not to work or keep up normal activity; 50 is needing considerable help and frequent medical care.
Studies often ask for 60 or 70 and above. Your doctor gives the score.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CTCAE grade
The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.
“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
nab-paclitaxel 100-240 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle.
Drug: nab-paclitaxel
nab-paclitaxel 120 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Drug: nab-paclitaxel
nab-paclitaxel 150 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Drug: nab-paclitaxel
nab-paclitaxel 180 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Drug: nab-paclitaxel
nab-paclitaxel 210 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Drug: nab-paclitaxel
nab-paclitaxel 240 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Drug: nab-paclitaxel
nab-paclitaxel 270 mg/m\^2 IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity to establish the RP2D.
Drug: nab-paclitaxel
Participants with Ewing's sarcoma: nab-paclitaxel at the RP2D (240 mg/m\^2 in participants weighing \> 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
Drug: nab-paclitaxel
Participants with neuroblastoma: nab-paclitaxel at the RP2D (240 mg/m\^2 in participants weighing \> 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
Drug: nab-paclitaxel
Participants with rhabdomyosarcoma: nab-paclitaxel at the RP2D (240 mg/m\^2 in participants weighing \> 10 kg and 11.5 mg/kg in participants weighing ≤ 10 kg) IV on Days 1, 8 and 15 of a 28-day cycle until disease progression, death, withdrawal of consent, or unacceptable toxicity.
Drug: nab-paclitaxel
nab-paclitaxel 120-270 mg/m2 IV on Days 1, 8 and 15 of a 28-day cycle
Also known as: Abraxane
IV infusion
Also known as: Abraxane
Phase 1: Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted \> 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted \> 7 days or required transfusion \> 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting \> 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay \> 21 days. Use of "..." in the table rows signifies the continuation of row title per the above list.
Time frame: DLT assessment period: For participants > 10 kg: the first 28-day cycle including Cycle 2 Day 1 predose evaluations; for participants ≤ 10 kg: the first two 28-day cycles including Cycle 3 Day 1 predose evaluations
Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0.
Time frame: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
Phase 2: Overall Response Rate (ORR)
Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
Phase 1: ORR
Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
Time frame: Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively.
Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax)
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: Cmax - Dose-Normalized
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: Area Under the Plasma Concentration-Time Curve (AUC)
Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: AUC - Dose-Normalized
Measurements include: AUC24 and AUCinf.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: Clearance (CL)
Measurement of renal clearance from the body.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: CL - Body Surface Area (BSA)-Normalized
Measurement of renal clearance from the body.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: Volume of Distribution (Vss)
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1: Vss - BSA-Normalized
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants <6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL)
Population PK analysis was performed using nonlinear mixed effect modeling.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3)
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.
Time frame: Cycle 1 Day 1 (Participants ≥ 6 years: 1-2 minutes prior to the end of infusion [EOI], and 15 minutes, 1, 3, 5, 8, 24, 48, and 72 hours after the EOI. Participants < 6 years: 1-2 minutes prior to the EOI, and 15 minutes, 3, 5, and 24 hours after the EOI.)
Phase 2: Duration of Response (DOR)
Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.
Phase 2: Disease Control Rate (DCR)
Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13).
Phase 2: Progression-Free Survival (PFS)
PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed until disease progression (if applicable) up to a maximum of 100.3 weeks.
Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year
Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
Time frame: 1 year
Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
Time frame: Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), Rhabdomyosarcoma = 5 weeks (1-13). Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
| Milestone | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Started | 16 | 8 | 14 | 11 | 8 | 7 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 16 | 8 | 14 | 11 | 8 | 7 | 0 | 0 | 0 |
| Withdrew: Adverse event | 4 | 0 | 2 | 1 | 2 | 2 | 0 | 0 | 0 |
| Withdrew: Progressive disease | 8 | 6 | 8 | 4 | 5 | 4 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by parent/guardian | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Physician decision | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Symptomatic deterioration | 3 | 2 | 2 | 2 | 1 | 1 | 0 | 0 | 0 |
| Withdrew: Miscellaneous | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 14 | 14 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 14 | 14 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 |
| Withdrew: Progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 12 | 11 |
| Withdrew: Symptomatic deterioration | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 |
A DLT was defined as investigational product (IP)-related adverse events occurring during the DLT assessment period that led to treatment discontinuation or met one of the following criteria: - Common Terminology Criteria for Adverse Events (CTCAE) Grade (Gr) 3 or 4 nonhematologic toxicity (excluding transient transaminitis) - CTCAE Gr 3 or 4 nausea or vomiting that persisted \> 5 days despite maximal anti-emetic treatment - CTCAE Gr 4 thrombocytopenia or anemia that persisted \> 7 days or required transfusion \> 7 days - CTCAE Gr 3 thrombocytopenia with bleeding - CTCAE Gr 4 uncomplicated neutropenia lasting \> 7 days - Febrile neutropenia with confirmed bacterial infection - CTCAE Gr 3 hematologic toxicity requiring treatment (tx) delay \> 21 days. Use of "..." in the table rows signifies the continuation of row title per the above list.
| Participants | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| At least 1 DLT | 1 | 0 | 0 | 0 | 0 | 1 |
| Gr 3/4 Nonhematologic Toxicity... | 1 | 0 | 0 | 0 | 0 | 0 |
| Gr 3/4 Nausea or Vomiting Persisting >5 days... | 0 | 0 | 0 | 0 | 0 | 0 |
| Gr 4 Thrombocytopenia/Anemia Persisting >7 days... | 0 | 0 | 0 | 0 | 0 | 0 |
| Gr 3 Thrombocytopenia with Bleeding | 0 | 0 | 0 | 0 | 0 | 0 |
| Gr 4 Uncomplicated Neutropenia Lasting >7 days | 0 | 0 | 0 | 0 | 0 | 1 |
| Febrile Neutropenia+Confirmed Bacterial Infection | 0 | 0 | 0 | 0 | 0 | 0 |
| Gr3 Hematologic Toxicity Requiring Tx Delay... | 0 | 0 | 0 | 0 | 0 | 0 |
An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A serious AE (SAE) is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of an AE was graded according to the CTCAE, Version 4.0.
| Participants | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| TEAE | 16 | 8 | 14 | 11 | 8 | 7 |
| Treatment-related (TR) TEAE | 14 | 8 | 12 | 11 | 7 | 7 |
| Grade 3 or 4 TEAE | 13 | 8 | 10 | 10 | 8 | 7 |
| TR Grade 3 or 4 TEAE | 9 | 7 | 7 | 9 | 7 | 7 |
| Serious TEAE | 10 | 7 | 6 | 5 | 3 | 4 |
| TR Serious TEAE | 1 | 4 | 4 | 2 | 1 | 3 |
| TEAE Leading to Drug Discontinuation | 4 | 0 | 2 | 1 | 2 | 2 |
| TR TEAE Leading to Drug Discontinuation | 1 | 0 | 0 | 1 | 2 | 2 |
| TEAE Leading to Dose Reduction | 0 | 1 | 2 | 1 | 3 | 3 |
| TR TEAE Leading to Dose Reduction | 0 | 1 | 2 | 1 | 3 | 3 |
| TEAE Leading to Drug Interruption | 2 | 2 | 3 | 4 | 3 | 2 |
| TR TEAE Leading to Drug Interruption | 0 | 2 | 1 | 3 | 3 | 2 |
| TEAE Leading to Death | 2 | 1 | 0 | 0 | 1 | 1 |
| TR TEAE Leading to Death | 0 | 0 | 0 | 0 | 0 | 0 |
Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. (For Phase 2 neuroblastoma participants who had both RECIST and Curie Score tumor evaluations, both tumor response results were considered and an overall response was derived.) Confidence interval was obtained using the Clopper-Pearson method.
| percentage of participants | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|
| Phase 2: Overall Response Rate (ORR) | 0 (0.0 to 24.7) | 0 (0.0 to 23.2) | 7.1 (0.2 to 33.9) |
Overall response rate was defined as the percentage of participants who achieved a complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions) confirmed no less than 4 weeks after the criteria for response were first met) using RECIST version 1.1 guidelines over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
| percentage of participants | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: ORR | 0 (0.0 to 23.2) | 0 (0.0 to 36.9) | 0 (0.0 to 26.5) | 0 (0.0 to 30.8) | 12.5 (0.3 to 52.7) | 14.3 (0.4 to 57.9) |
| ng/mL | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: Maximum Observed Concentration of Paclitaxel in Blood Plasma (Cmax) | 3488 ± 73.7 | 5468 ± 38.0 | 5597 ± 33.4 | 5616 ± 63.9 | 7831 ± 23.1 | 8078 ± 41.5 |
| ng/mL/[mg] | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: Cmax - Dose-Normalized | 23.3 ± 87.5 | 25.4 ± 46.6 | 27.3 ± 47.3 | 23.2 ± 80.3 | 28.2 ± 48.7 | 21.0 ± 46.6 |
Measurements include: AUC from time zero to the last measurable concentration (AUCt), AUC from time zero to 24 hours (AUC24), and AUC from time zero to infinity (AUCinf).
| ng*h/mL | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| AUCt | 7844 ± 73.4 | 10374 ± 91.8 | 9690 ± 37.1 | 11817 ± 64.0 | 12706 ± 29.2 | 11245 ± 22.6 |
| AUC24 | 6392 ± 79.0 | 8944 ± 85.9 | 8365 ± 37.7 | 10932 ± 66.3 | 11167 ± 27.4 | 9768 ± 20.7 |
| AUCinf | 8867 ± 85.4 | 11992 ± 99.8 | 10087 ± 38.4 | 14361 ± 72.1 | 14242 ± 29.2 | 12424 ± 28.5 |
Measurements include: AUC24 and AUCinf.
| ng*h/mL/[mg] | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| AUC24 | 42.7 ± 77.4 | 41.6 ± 87.0 | 40.8 ± 39.7 | 43.3 ± 63.6 | 40.2 ± 65.4 | 25.4 ± 26.1 |
| AUCinf | 62.0 ± 75.7 | 49.2 ± 101 | 47.8 ± 39.8 | 64.8 ± 25.4 | 52.3 ± 67.4 | 31.3 ± 34.9 |
Measurement of renal clearance from the body.
| L/h | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: Clearance (CL) | 16.1 ± 75.6 | 20.3 ± 101 | 20.9 ± 39.9 | 15.4 ± 25.4 | 19.1 ± 67.4 | 31.9 ± 35.0 |
Measurement of renal clearance from the body.
| L/h/m^2 | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: CL - Body Surface Area (BSA)-Normalized | 13.5 ± 85.1 | 12.5 ± 99.3 | 17.8 ± 38.3 | 14.6 ± 72.3 | 16.7 ± 29.2 | 21.8 ± 28.4 |
| liters | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: Volume of Distribution (Vss) | 127 ± 145 | 266 ± 78.3 | 146 ± 106 | 89.8 ± 45.1 | 175 ± 117 | 446 ± 17.6 |
| L/m^2 | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 |
|---|---|---|---|---|---|---|
| Phase 1: Vss - BSA-Normalized | 106 ± 95.3 | 164 ± 78.4 | 124 ± 82.8 | 84.9 ± 49.7 | 154 ± 56.5 | 304 ± 29.0 |
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V1 was 0.888.
| liters | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Volume of Distribution of the Central Compartment (V1) | 11.8 |
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for VMEL was 1.12.
| μg/h | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Maximum Elimination Rate From the Central Compartment (VMEL) | 31983 |
Population PK analysis was performed using nonlinear mixed effect modeling.
| μg/L | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Concentration in the Central Compartment at 50% of VMEL (KMEL) | 951 |
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q2 was 1.12.
| L/h | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the First Peripheral Compartment (Q2) | 22.4 |
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for Q3 was 1.12.
| L/h | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Intercompartmental CL Between the Central Compartment and the Second Peripheral Compartment (Q3) | 34.8 |
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V2 was 0.888.
| liters | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Volume of Distribution of the First Peripheral Compartment (V2) | 545 |
Population PK analysis was performed using nonlinear mixed effect modeling. The estimated allometric function for V3 was 0.888.
| liters | PK Population |
|---|---|
| Phase 1 and 2 Population PK: Volume of Distribution of the Second Peripheral Compartment (V3) | 45.3 |
Duration of response was defined as the time from the date of the first response (CR/PR, using RECIST version 1.1 guidelines) to disease progression for participants with a confirmed CR or PR. Participants who did not have disease progression or had not died were censored at the time of their last disease assessment or at time of start of new anticancer therapy, whichever occurred first. (For Phase 2 neuroblastoma patients who had both RECIST version 1.1 and Curie Score tumor evaluations, both tumor responses results were considered and an overall response was derived.)
| weeks | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|
| Phase 2: Duration of Response (DOR) | — | — | 6.14 (6.14 to 6.14) |
Disease control rate was defined as the percentage of participants who achieved either a stable disease maintained for ≥ 16 weeks or confirmed CR (confirmed no less than 4 weeks after criteria for response were first met) or confirmed PR (confirmed no less than 4 weeks after criteria for response were first met) over the total number of participants available for the analysis. Confidence interval was obtained using the Clopper-Pearson method.
| percentage of participants | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|
| Phase 2: Disease Control Rate (DCR) | 30.8 (9.1 to 61.4) | 7.1 (0.2 to 33.9) | 7.1 (0.2 to 33.9) |
PFS was defined as the time from the first dose date to the start of disease progression or participant death (any cause), whichever occurred first. Disease progression was classed as either a disease progression observed as a response assessment, or a disease progression or symptomatic deterioration at treatment/study discontinuation. Participants who did not have disease progression or had not died were censored at the last known time that the participant was progression free. Disease progression was considered according to RECIST version 1.1 for Phase 2 Ewing's sarcoma and rhabdomyosarcoma participants. (For Phase 2 neuroblastoma participants who had both RECIST 1.1 and Curie score tumor evaluations, both tumor responses results were considered and an overall response was derived.) Median PFS time was estimated through Kaplan-Meier methods. 95% confidence interval about the median time to PFS event was obtained using Greenwood's method.
| weeks | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|
| Phase 2: Progression-Free Survival (PFS) | 13 (7.4 to 16.1) | 7.4 (4.6 to 8.1) | 5.1 (2.1 to 7.9) |
Overall survival was defined as the time from the first dose date to date of death (any cause). Participants who were alive were censored at the last known time that the participant was alive.
| percentage of participants | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|
| Phase 2: Kaplan-Meier Estimate of Overall Survival Rate at 1 Year | 48 (14 to 76) | 25 (4 to 54) | 15 (2 to 39) |
An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A SAE is any AE occurring at any dose that: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. TEAEs were defined as AEs that began or worsened in severity on or after the date of the first dose of study drug and within 28 days of the date of the last dose of study drug. The severity of the AEs was graded according to the Common Terminology Criteria for Adverse Events, Version 4.0. Participants were followed for 28 days after discontinuing treatment for safety and monitoring of AEs.
| Participants | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma |
|---|---|---|---|
| TEAE | 14 | 14 | 14 |
| Treatment-related (TR) TEAE | 13 | 12 | 12 |
| Grade 3 or 4 TEAE | 12 | 13 | 12 |
| TR Grade 3 or 4 TEAE | 9 | 9 | 10 |
| Serious TEAE | 6 | 6 | 11 |
| TR Serious TEAE | 2 | 2 | 6 |
| TEAE Leading to Drug Discontinuation | 3 | 1 | 3 |
| TR TEAE Leading to Drug Discontinuation | 1 | 0 | 3 |
| TEAE Leading to Dose Reduction | 4 | 5 | 4 |
| TR TEAE Leading to Dose Reduction | 4 | 4 | 4 |
| TEAE Leading to Drug Interruption | 5 | 3 | 4 |
| TR TEAE Leading to Drug Interruption | 3 | 3 | 2 |
| TEAE Leading to Death | 0 | 2 | 3 |
| TR TEAE Leading to Death | 0 | 0 | 0 |
Collected over Median treatment duration in Phase 1 was 7.0 weeks, with minimum and maximum duration of 1 and 49 weeks, respectively. Median treatment duration in Phase 2 per group: Ewings Sarcoma = 14 weeks (3-31), Neuroblastoma = 7 weeks (3-23), rhabdomyosarcoma = 5 weeks (1-13).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Phase 1: Nab-Paclitaxel 120 mg/m^2 | 14/16 (87.5%) | 10/16 (62.5%) | 16/16 (100%) |
| Phase 1: Nab-Paclitaxel 150 mg/m^2 | 7/8 (87.5%) | 7/8 (87.5%) | 8/8 (100%) |
| Phase 1: Nab-Paclitaxel 180 mg/m^2 | 11/14 (78.6%) | 6/14 (42.9%) | 14/14 (100%) |
| Phase 1: Nab-Paclitaxel 210 mg/m^2 | 5/11 (45.5%) | 5/11 (45.5%) | 11/11 (100%) |
| Phase 1: Nab-Paclitaxel 240 mg/m^2 | 8/8 (100%) | 3/8 (37.5%) | 8/8 (100%) |
| Phase 1: Nab-Paclitaxel 270 mg/m^2 | 5/7 (71.4%) | 4/7 (57.1%) | 7/7 (100%) |
| Phase 2: Nab-Paclitaxel 240 mg/m^2 | 25/42 (59.5%) | 23/42 (54.8%) | 42/42 (100%) |
| Event | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Nab-Paclitaxel 240 mg/m^2 |
|---|---|---|---|---|---|---|---|
| PyrexiaGeneral disorders | 0/16 | 3/8 | 2/14 | 3/11 | 1/8 | 2/7 | 6/42 |
| HyponatraemiaMetabolism and nutrition disorders | 0/16 | 2/8 | 0/14 | 0/11 | 0/8 | 0/7 | 0/42 |
| Febrile neutropeniaBlood and lymphatic system disorders | 0/16 | 0/8 | 1/14 | 0/11 | 0/8 | 1/7 | 4/42 |
| NauseaGastrointestinal disorders | 0/16 | 0/8 | 0/14 | 0/11 | 0/8 | 1/7 | 0/42 |
| VomitingGastrointestinal disorders | 0/16 | 1/8 | 1/14 | 0/11 | 0/8 | 1/7 | 1/42 |
| PneumoniaInfections and infestations | 0/16 | 0/8 | 0/14 | 0/11 | 0/8 | 1/7 | 0/42 |
| Osteosarcoma metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/16 | 0/8 | 0/14 | 0/11 | 0/8 | 1/7 | 0/42 |
| ThrombocytopeniaBlood and lymphatic system disorders | 0/16 | 1/8 | 0/14 | 0/11 | 0/8 | 0/7 | 2/42 |
| TachycardiaCardiac disorders | 0/16 | 1/8 | 0/14 | 0/11 | 0/8 | 0/7 | 0/42 |
| Abdominal painGastrointestinal disorders | 0/16 | 1/8 | 0/14 | 0/11 | 0/8 | 0/7 | 1/42 |
| Event | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Nab-Paclitaxel 240 mg/m^2 |
|---|---|---|---|---|---|---|---|
| NeutropeniaBlood and lymphatic system disorders | 7/16 | 4/8 | 6/14 | 8/11 | 7/8 | 6/7 | 23/42 |
| AnaemiaBlood and lymphatic system disorders | 8/16 | 6/8 | 6/14 | 5/11 | 6/8 | 6/7 | 27/42 |
| LeukopeniaBlood and lymphatic system disorders | 6/16 | 1/8 | 2/14 | 5/11 | 5/8 | 3/7 | 18/42 |
| ThrombocytopeniaBlood and lymphatic system disorders | 1/16 | 2/8 | 2/14 | 1/11 | 2/8 | 4/7 | 8/42 |
| ConstipationGastrointestinal disorders | 4/16 | 3/8 | 3/14 | 6/11 | 2/8 | 1/7 | 10/42 |
| DiarrhoeaGastrointestinal disorders | 2/16 | 4/8 | 4/14 | 3/11 | 4/8 | 2/7 | 8/42 |
| VomitingGastrointestinal disorders | 8/16 | 3/8 | 2/14 | 3/11 | 3/8 | 1/7 | 14/42 |
| PyrexiaGeneral disorders | 6/16 | 3/8 | 5/14 | 5/11 | 4/8 | 2/7 | 14/42 |
| Blood alkaline phosphatase increasedInvestigations | 0/16 | 4/8 | 0/14 | 1/11 | 0/8 | 0/7 | 1/42 |
| HyponatraemiaMetabolism and nutrition disorders | 1/16 | 4/8 | 1/14 | 0/11 | 0/8 | 1/7 | 1/42 |
| Age, Continuous(years) | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 11.7 ± 3.32 | 12.1 ± 5.84 | 10.2 ± 4.64 | 10.2 ± 5.36 | 11.6 ± 4.63 | 12.1 ± 2.97 | 10.1 ± 4.63 | 7.1 ± 3.42 | 12.4 ± 6.42 | 10.7 ± 4.81 |
| Sex: Female, Male(Participants) | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 9 | 4 | 9 | 7 | 1 | 3 | 6 | 5 | 9 | 53 |
| Male | 7 | 4 | 5 | 4 | 7 | 4 | 8 | 9 | 5 | 53 |
| Ethnicity (NIH/OMB)(Participants) | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 3 | 1 | 1 | 3 | 0 | 0 | 2 | 5 | 17 |
| Not Hispanic or Latino | 6 | 5 | 7 | 10 | 5 | 5 | 11 | 8 | 8 | 65 |
| Unknown or Not Reported | 8 | 0 | 6 | 0 | 0 | 2 | 3 | 4 | 1 | 24 |
| Race/Ethnicity, Customized(Participants) | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| White | 11 | 8 | 9 | 9 | 8 | 5 | 11 | 11 | 12 | 84 |
| Not Collected or Reported | 5 | 0 | 5 | 0 | 0 | 1 | 3 | 3 | 1 | 18 |
| Other, Not Specified | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 3 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Participants With Any Prior Cancer Treatment(Participants) | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Any Prior Cancer Treatment | 16 | 8 | 14 | 11 | 8 | 7 | 14 | 14 | 14 | 106 |
| Prior Radiation Therapy | 9 | 4 | 11 | 7 | 6 | 6 | 12 | 10 | 10 | 75 |
| Prior Cancer Surgeries | 14 | 7 | 9 | 9 | 5 | 7 | 10 | 11 | 6 | 78 |
| Prior Systemic Anticancer Therapy | 16 | 8 | 14 | 11 | 8 | 7 | 14 | 14 | 14 | 106 |
| Prior Systemic Anticancer Regimens | 16 | 8 | 14 | 11 | 8 | 7 | 14 | 14 | 14 | 106 |
| Prior Stem Cell Transplants | 2 | 2 | 3 | 2 | 3 | 2 | 3 | 10 | 0 | 27 |
| Other Prior Anticancer Therapies | 2 | 0 | 1 | 3 | 2 | 0 | 1 | 6 | 0 | 15 |
| Number of Prior Systemic Anticancer Regimens Received(systemic anticancer regimens) | Phase 1: Nab-Paclitaxel 120 mg/m^2 | Phase 1: Nab-Paclitaxel 150 mg/m^2 | Phase 1: Nab-Paclitaxel 180 mg/m^2 | Phase 1: Nab-Paclitaxel 210 mg/m^2 | Phase 1: Nab-Paclitaxel 240 mg/m^2 | Phase 1: Nab-Paclitaxel 270 mg/m^2 | Phase 2: Ewing's Sarcoma | Phase 2: Neuroblastoma | Phase 2: Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 3.69 ± 1.815 | 3.25 ± 1.832 | 3.64 ± 1.946 | 3.64 ± 2.461 | 3.00 ± 1.309 | 3.00 ± 0.816 | 2.50 ± 0.519 | 2.14 ± 0.663 | 2.21 ± 0.579 | 2.99 ± 1.552 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Dec 2013 to primary completion in Dec 2017, 48 months.
Results were first posted in Dec 2018, 1 year after primary completion.
Of 35 phase 1/2 interventional studies under Neuroblastoma, half reached primary completion within 80 months of starting (the median), counting those still running; a quarter within 62 and three quarters within 115. This study's 48 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Dec 2019. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Albumin-Bound Paclitaxel