A Phase 1/2 interventional study of Adavosertib and Irinotecan Hydrochloride in Central Nervous System Embryonal Tumor With Rhabdoid Features, Central Nervous System Embryonal Tumor, Not Otherwise Specified and Central Nervous System Ganglioneuroblastoma, sponsored by National Cancer Institute (NCI). Completed at 24 sites in 2 countries. Open to participants aged 1 Year to 21 Years. Per ClinicalTrials.gov, last updated 2023-09-26.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
This phase I/II trial studies the side effects and best dose of adavosertib and irinotecan hydrochloride in treating younger patients with solid tumors that have come back (relapsed) or that have not responded to standard therapy (refractory). Adavosertib and irinotecan hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To estimate the maximum tolerated dose (MTD) and/or recommended phase 2 dose of adavosertib (AZD1755 [MK-1775]) administered on days 1 through 5 every 21 days, in combination with oral irinotecan (irinotecan hydrochloride), to children with recurrent or refractory solid tumors.
II. To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
III. To characterize the pharmacokinetics of AZD1755 (MK-1775) in children with refractory cancer.
SECONDARY OBJECTIVES:
I. To preliminarily define the antitumor activity of AZD1755 (MK-1775) and irinotecan within the confines of a Phase 1 study.
II. To obtain initial phase 2 efficacy data on the anti-tumor activity of AZD1755 (MK-1775) in combination with irinotecan administered to children with relapsed or refractory neuroblastoma, in children with relapsed or refractory medulloblastoma/CNS PNET (central nervous system primitive neuroectodermal tumor) and in children with relapsed or refractory rhabdomyosarcoma.
III. To investigate checkpoint over-ride by AZD1755 (MK-1775) via the mechanism-based pharmacodynamic (PD) biomarker of decreased cyclin-dependent kinase 1 (CDK1) phosphorylation in correlative and exploratory studies.
IV. To evaluate potential predictive biomarkers of AZD1755 (MK-1775) sensitivity, including v-myc avian myelocytomatosis viral oncogene homolog (MYC), v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN), phosphorylated-WEE1 G2 checkpoint kinase (p-Wee1), enhancer of zeste homolog 2 (Drosophila) (EZH2) and gamma-H2A histone family, member gamma-(H2AX) in tumor tissues in correlative and exploratory studies.
OUTLINE: This is a phase I, dose-escalation followed by a phase II study.
Patients receive irinotecan hydrochloride orally (PO) and adavosertib PO on days 1-5. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically.
120 studies on the registry are indexed under Neuroectodermal Tumors, Primitive; 22 are open to participants now.
This study's enrollment of 76 is above the median of 35 across 88 interventional studies indexed under Neuroectodermal Tumors, Primitive.
Browse Neuroectodermal Tumors, Primitive studies →National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.
Of its 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.
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.
or radioisotope (GFR) >= 70 ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
Exclusion Criteria:
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.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
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 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.
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).
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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 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.
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.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
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.
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 have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask 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.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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.
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.
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.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
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.
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.
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.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
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.
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.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask 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.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GVHD (graft-versus-host disease)
After a transplant from a donor, the donor’s immune cells attack the recipient’s body, often the skin, gut or liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients receive irinotecan hydrochloride PO and adavosertib PO on days 1-5. Treatment repeats every 21 days for up to 18 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Adavosertib · Drug: Irinotecan Hydrochloride
Given PO
Also known as: AZD-1775, AZD1775, MK-1775, MK1775
Given PO
Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E
Maximum Tolerated Dose (MTD)
MTD is defined as the maximum doses of adavosertib and irinotecan hydrochloride at which fewer than one-third of patients experience dose limiting toxicities when receiving this combination.
Time frame: Up to 21 days
Number of Participants With Cycle 1 DLT
To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
Time frame: Up to 21 days
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, AUC
The PK parameters will be summarized by means and standard deviations
Time frame: Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Cmax
The PK parameters will be summarized by means and standard deviations
Time frame: Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, HL-Lambda (Half Life)
The PK parameters will be summarized by means and standard deviations
Time frame: Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Tmax
The PK parameters will be summarized by means and standard deviations
Time frame: Cycle 1 day 1 prior to the irinotecan infusion, prior to the adavosertib dose, 4 hours after the dose of adavosertib is given, and prior to the irinotecan dose on day 2
Number and Percentage of Participants With Best Overall Response With Partial or Complete Response
Frequency (%) of response-evaluable patients with best overall response of partial or complete response as determined by revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
Time frame: Up to 1 year
Mean Fold Change in Gamma H2AX in Peripheral Blood Mono Nuclear Cells
Mean (SD) of the increase in gamma H2AX at 4 hours versus baseline among patients in Part A stratified by dose level.
Time frame: Up to 1 day
Number and Percentage of Part B Neuroblastoma Participants With MYCN Amplification
Frequency (%) of Part B Neuroblastoma participants with MYCN amplification.
Time frame: Assessed at Baseline
| Milestone | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Started | 4 | 5 | 4 | 10 | 8 | 6 | 19 | 10 | 10 |
| Completed | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 |
| Not completed | 4 | 5 | 4 | 10 | 7 | 6 | 18 | 9 | 10 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Withdrew: Death | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Withdrew: Lack of efficacy | 3 | 5 | 2 | 8 | 3 | 6 | 10 | 9 | 8 |
| Withdrew: Physician decision | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 |
| Withdrew: Withdrawal by subject | 0 | 0 | 2 | 2 | 3 | 0 | 5 | 0 | 0 |
MTD is defined as the maximum doses of adavosertib and irinotecan hydrochloride at which fewer than one-third of patients experience dose limiting toxicities when receiving this combination.
| mg/m^2 | Part A |
|---|---|
| Irinotecan (IRIN) | 90 |
| AZD1775 (MK-1775) | 85 |
To define and describe the toxicities of AZD1755 (MK-1775) in combination with oral irinotecan administered on this schedule.
| Participants | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Cycle 1 DLT | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 1 |
The PK parameters will be summarized by means and standard deviations
| hr*nmol/L | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion |
|---|---|---|---|---|---|---|
| Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, AUC | 3222.95 ± 1770.92 | 3397.3 ± 2404.13 | 4413.22 ± 2026.63 | 5344.96 ± 1839.62 | 5161.36 ± 3282.31 | 4655.13 ± 1943.68 |
The PK parameters will be summarized by means and standard deviations
| nmol/L | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion |
|---|---|---|---|---|---|---|
| Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Cmax | 443.96 ± 168.13 | 511.23 ± 341.4 | 539.84 ± 265.58 | 652.71 ± 240.27 | 733.59 ± 397.41 | 590.28 ± 378.65 |
The PK parameters will be summarized by means and standard deviations
| hours | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion |
|---|---|---|---|---|---|---|
| Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, HL-Lambda (Half Life) | 4.7 ± 1 | 5.5 ± 3.9 | 5.7 ± 1.3 | 4.9 ± 1 | 4 ± 2.1 | 4.7 ± 0.6 |
The PK parameters will be summarized by means and standard deviations
| hours | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion |
|---|---|---|---|---|---|---|
| Pharmacokinetic (PK) Parameters of Adavosertib in Terms of Systemic Exposure, Tmax | 3.5 ± 3 | 2 ± 1.3 | 3 ± 1.1 | 3 ± 1.1 | 2.4 ± 0.9 | 3.5 ± 3 |
Frequency (%) of response-evaluable patients with best overall response of partial or complete response as determined by revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1).
| Participants | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Number and Percentage of Participants With Best Overall Response With Partial or Complete Response | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 2 | 0 |
Mean (SD) of the increase in gamma H2AX at 4 hours versus baseline among patients in Part A stratified by dose level.
| Fold change | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 |
|---|---|---|---|---|---|
| Mean Fold Change in Gamma H2AX in Peripheral Blood Mono Nuclear Cells | 4.5 ± 4.18 | 0.45 ± 0.24 | 3.78 ± 0.72 | 2 ± 2.17 | 10 ± 11.89 |
Frequency (%) of Part B Neuroblastoma participants with MYCN amplification.
| Participants | Part B, Neuroblastoma |
|---|---|
| Number and Percentage of Part B Neuroblastoma Participants With MYCN Amplification | 2 |
Collected over Up to 12 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A, Dose Level 1 | 1/4 (25%) | 4/4 (100%) | 4/4 (100%) |
| Part A, Dose Level 2 | 0/5 (0%) | 2/5 (40%) | 5/5 (100%) |
| Part A, Dose Level 3 | 0/4 (0%) | 3/4 (75%) | 4/4 (100%) |
| Part A, Dose Level 4 | 0/10 (0%) | 10/10 (100%) | 10/10 (100%) |
| Part A, Dose Level 5 | 0/8 (0%) | 6/8 (75%) | 8/8 (100%) |
| Part A, PK Expansion | 0/6 (0%) | 6/6 (100%) | 6/6 (100%) |
| Part B, Neuroblastoma | 1/19 (5.3%) | 11/19 (57.9%) | 19/19 (100%) |
| Part C, Medulloblastoma/CNS PNET | 1/10 (10%) | 9/10 (90%) | 10/10 (100%) |
| Part D, Rhabdomyosarcoma | 1/10 (10%) | 7/10 (70%) | 10/10 (100%) |
| Event | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| Lymphocyte count decreasedInvestigations | 1/4 | 2/5 | 1/4 | 7/10 | 1/8 | 2/6 | 5/19 | 2/10 | 1/10 |
| Neutrophil count decreasedInvestigations | 2/4 | 0/5 | 2/4 | 5/10 | 2/8 | 1/6 | 6/19 | 6/10 | 3/10 |
| Hearing impairedEar and labyrinth disorders | 0/4 | 0/5 | 0/4 | 1/10 | 0/8 | 0/6 | 3/19 | 4/10 | 0/10 |
| DiarrheaGastrointestinal disorders | 1/4 | 0/5 | 0/4 | 1/10 | 3/8 | 1/6 | 0/19 | 1/10 | 1/10 |
| HypokalemiaMetabolism and nutrition disorders | 0/4 | 0/5 | 0/4 | 1/10 | 3/8 | 1/6 | 0/19 | 1/10 | 1/10 |
| White blood cell decreasedInvestigations | 1/4 | 0/5 | 1/4 | 3/10 | 1/8 | 1/6 | 3/19 | 3/10 | 0/10 |
| Platelet count decreasedInvestigations | 1/4 | 0/5 | 0/4 | 1/10 | 0/8 | 0/6 | 5/19 | 1/10 | 0/10 |
| AnemiaBlood and lymphatic system disorders | 0/4 | 0/5 | 1/4 | 2/10 | 1/8 | 0/6 | 3/19 | 1/10 | 2/10 |
| DehydrationMetabolism and nutrition disorders | 0/4 | 1/5 | 0/4 | 0/10 | 2/8 | 0/6 | 0/19 | 0/10 | 1/10 |
| DysarthriaNervous system disorders | 0/4 | 0/5 | 1/4 | 1/10 | 0/8 | 0/6 | 0/19 | 0/10 | 0/10 |
| Event | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma |
|---|---|---|---|---|---|---|---|---|---|
| AlopeciaSkin and subcutaneous tissue disorders | 2/4 | 4/5 | 4/4 | 5/10 | 6/8 | 1/6 | 2/19 | 4/10 | 3/10 |
| AnemiaBlood and lymphatic system disorders | 4/4 | 3/5 | 2/4 | 9/10 | 6/8 | 3/6 | 14/19 | 8/10 | 7/10 |
| DiarrheaGastrointestinal disorders | 3/4 | 5/5 | 3/4 | 8/10 | 6/8 | 5/6 | 11/19 | 7/10 | 7/10 |
| FatigueGeneral disorders | 3/4 | 2/5 | 4/4 | 6/10 | 6/8 | 4/6 | 8/19 | 7/10 | 8/10 |
| Lymphocyte count decreasedInvestigations | 4/4 | 4/5 | 4/4 | 8/10 | 5/8 | 4/6 | 12/19 | 8/10 | 8/10 |
| VomitingGastrointestinal disorders | 2/4 | 5/5 | 3/4 | 8/10 | 6/8 | 3/6 | 13/19 | 10/10 | 8/10 |
| Abdominal painGastrointestinal disorders | 2/4 | 4/5 | 3/4 | 5/10 | 4/8 | 2/6 | 3/19 | 4/10 | 7/10 |
| Alanine aminotransferase increasedInvestigations | 2/4 | 1/5 | 1/4 | 4/10 | 4/8 | 2/6 | 10/19 | 8/10 | 2/10 |
| HypoalbuminemiaMetabolism and nutrition disorders | 1/4 | 1/5 | 2/4 | 4/10 | 2/8 | 2/6 | 6/19 | 3/10 | 8/10 |
| NauseaGastrointestinal disorders | 2/4 | 3/5 | 3/4 | 5/10 | 5/8 | 4/6 | 12/19 | 8/10 | 7/10 |
| Age, Categorical(Participants) | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 3 | 4 | 4 | 7 | 6 | 4 | 18 | 8 | 10 | 64 |
| Between 18 and 65 years | 1 | 1 | 0 | 3 | 2 | 2 | 1 | 2 | 0 | 12 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(Years) | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Median | 15 (10 to 19) | 16 (7 to 19) | 13.5 (11 to 15) | 11 (7 to 20) | 14.5 (5 to 20) | 10.5 (2 to 19) | 9 (6 to 19) | 13.5 (6 to 20) | 11 (4 to 16) | 11.5 (2 to 20) |
| Sex: Female, Male(Participants) | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 2 | 2 | 2 | 2 | 5 | 3 | 7 | 6 | 2 | 31 |
| Male | 2 | 3 | 2 | 8 | 3 | 3 | 12 | 4 | 8 | 45 |
| Ethnicity (NIH/OMB)(Participants) | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 1 | 0 | 0 | 1 | 2 | 0 | 1 | 1 | 2 | 8 |
| Not Hispanic or Latino | 3 | 5 | 4 | 9 | 6 | 6 | 16 | 9 | 7 | 65 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 3 |
| Race (NIH/OMB)(Participants) | Part A, Dose Level 1 | Part A, Dose Level 2 | Part A, Dose Level 3 | Part A, Dose Level 4 | Part A, Dose Level 5 | Part A, PK Expansion | Part B, Neuroblastoma | Part C, Medulloblastoma/CNS PNET | Part D, Rhabdomyosarcoma | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Asian | 0 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 0 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Black or African American | 0 | 0 | 0 | 1 | 0 | 2 | 4 | 3 | 0 | 10 |
| White | 4 | 4 | 1 | 8 | 5 | 4 | 11 | 7 | 9 | 53 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 1 | 1 | 0 | 1 | 0 | 3 | 0 | 1 | 7 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Mar 2014 to primary completion in Dec 2020, 81 months.
Results were first posted in Oct 2022, 1 year 9 months after primary completion.
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Studies of the drug tested here: Adavosertib
Neuroectodermal Tumors, Primitive →
National Cancer Institute (NCI) →