A Phase 1 interventional study of palbociclib isethionate and pharmacological study in Childhood Choroid Plexus Tumor, Childhood Ependymoblastoma and Childhood Grade III Meningioma, sponsored by Pediatric Brain Tumor Consortium. Terminated at 11 sites in United States. Open to participants aged 4 Years to 21 Years. Per ClinicalTrials.gov, last updated 2021-03-02.
Sponsored by Pediatric Brain Tumor Consortium · Phase 1, Interventional, and Treatment
Among 12 studies in Choroid Plexus Neoplasms by Pediatric Brain Tumor Consortium — none open to participants now, none under way, none of them phase 3. Choroid Plexus Neoplasms · Pediatric Brain Tumor Consortium.
Among the 12 studies in Choroid Plexus Neoplasms by Pediatric Brain Tumor Consortium, this one is the only one that started in 2014, is one of 9 in phase 1, and was the 12th registered.
85 studies on the registry are indexed under Choroid Plexus Neoplasms; 2 are open to participants now.
This study's enrollment of 35 is close to the median of 33 across 60 interventional studies indexed under Choroid Plexus Neoplasms.
Browse Choroid Plexus Neoplasms studies →None of the 12 studies in Choroid Plexus Neoplasms by Pediatric Brain Tumor Consortium is open now.
Of the 1 Choroid Plexus Neoplasms studies recruiting now, 1 (100%) set no upper age limit and 0 (0%) stop at 75 or younger; 0 take children under 18; 0 take healthy volunteers.
This study: 4 Years to 21 Years · all sexes · no healthy volunteers.
The full table on the hub →12 studies; the count open now beside each. This study's row is marked.
First in 2000; this study’s year is marked. 1 started in 2014.
Median enrollment 33 across the 9 interventional studies, 38 across the 3 observational. Of the 11 that completed or were terminated, 1 (9%) have results posted.
Pediatric Brain Tumor Consortium is the lead sponsor of 31 studies on the registry; none are open to participants now.
Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.
None of the studies under way reaches primary completion within a year.
Among the 12 studies in Choroid Plexus Neoplasms by Pediatric Brain Tumor Consortium, from their registry updates:
Nothing recorded among them since 2026-09-25.
This phase I trial studies the side effects and best dose of palbociclib isethionate in treating younger patients with central nervous system tumors that have grown, come back, or not responded to treatment. Palbociclib isethionate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD)/phase II recommended dose and describe toxicities related to PD-0332991 (palbociclib isethionate) in children with retinoblastoma protein 1 (Rb1) positive recurrent, progressive or refractory primary central nervous system (CNS) tumors.
II. To determine plasma pharmacokinetics of PD-0332991 in children with Rb1positive recurrent, progressive or refractory primary CNS tumors.
SECONDARY OBJECTIVES:
I. To record preliminary evidence of efficacy of PD-0332991 in children with recurrent CNS tumors.
II. To evaluate cyclin-dependent kinase (CDK)4/6, cyclin D1-3, Ink4a-ARF copy-number variations in available tumor tissue by array comparative, genomic hybridization (aCGH).
III. To explore the potential relationships between the pharmacokinetics of PD-0332991 and pharmacodynamic response (e.g. percentage change in absolute neutrophil count [ANC], platelet counts).
IV. To explore the pharmacogenetic polymorphisms in PD-0332991 metabolizing enzymes and transporters and relate these polymorphisms to PD-0332991 pharmacokinetics.
OUTLINE: This is a dose-escalation study.
Patients receive palbociclib isethionate orally (PO) once daily (QD) on days 1-21. Treatment repeats every 4 weeks for 26 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
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.
Body surface area (BSA):
Radiotherapy: patients must have had their last fraction of:
* Focal irradiation > 2 weeks prior to enrollment
or radioisotope (GFR) >= 70 ml/min/1.73 m\^2 or a serum creatinine based on age/gender as follows:
Exclusion Criteria:
Patients who have received any of the following:
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 diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
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.
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.
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 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).
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.
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.
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.
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.
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.
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.
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.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Patients receive palbociclib isethionate PO QD on days 1-21. Treatment repeats every 4 weeks for 26 courses in the absence of disease progression or unacceptable toxicity.
Drug: palbociclib isethionate · Other: pharmacological study · Other: laboratory biomarker analysis
Given PO
Also known as: 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one, 827022-33-3, palbociclib, PD 0332991-0054, PD-0332991, PD-332991, PF-00080665-73
Correlative studies
Also known as: pharmacological studies
Correlative studies
This study also gives Palbociclib. No intervention listed here names it: that was found by reading the record.
Maximum Tolerated Dose (MTD) of Palbociclib in Stratum I
Rolling-6 design was used to estimate MTD. The MTD was empirically defined as the highest dose level at which six patients were treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level had been determined to be too toxic. Stratum I consisted of less-heavily pre-treated patients.
Time frame: 4 weeks
Maximum Tolerated Dose (MTD) of Palbociclib in Stratum II
Rolling-6 design was used to estimate MTD. The MTD was empirically defined as the highest dose level at which six patients were treated with at most one patient experiencing a DLT and the next higher dose level had been determined to be too toxic. Stratum II consisted of heavily pre-treated patients.
Time frame: 4 weeks
Number of Patients Who Experienced Dose Limiting Toxicities (DLTs)
DLTs were defined as any of the following adverse events that were at least possibly related to palbociclib that occurred during the first 4 weeks of therapy regardless of expectedness. Hematologic DLTs included grade 3 neutropenia with fever and sepsis, grade 3 thrombocytopenia and/or requiring a platelet transfusion on 2 separate days within a 7-day period, or any grade 4 hematologic toxicity except lymphopenia. Non-hematologic DLTs included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., nausea and vomiting of \< 5 days; diarrhea and/or electrolyte disturbances which have not been maximally treated; AST/ALT elevation that returns to levels meeting eligibility criteria within 7 days of study drug interruption and does not recur upon restarting drug), or any grade 2 non-hematologic toxicity that persists for \> 7 days and is considered medically significant or sufficiently intolerable by patients requires treatment interruption.
Time frame: 4 weeks
Single Dose Apparent Volume of Central Compartment (Vc/F)
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Apparent volume of central compartment (Vc/F) was estimated using a non-compartmental method.
Time frame: Up to day 3
Single Dose Elimination Rate Constant (Ke)
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Elimination rate constant (Ke) was estimated using a non-compartmental method.
Time frame: Up to day 3
Single Dose Half-life (t1/2)
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Half-life (t1/2) was estimated using a non-compartmental method.
Time frame: Up to day 3
Single Dose Apparent Oral Clearance (CL/F)
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Apparent oral clearance (CL/F) was estimated using a non-compartmental method.
Time frame: Up to day 3
Single Dose Area Under the Plasma Concentration Time Curve (AUC)
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Area under the plasma concentration time curve (AUC) was estimated using a non-compartmental method.
Time frame: Up to day 3
Steady State Apparent Volume of Central Compartment (Vc/F)
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Apparent volume of central compartment (Vc/F) was estimated using a non-compartmental method.
Time frame: Up to day 22
Steady State Elimination Rate Constant (Ke)
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Elimination rate constant (Ke) was estimated using a non-compartmental method.
Time frame: Up to day 22
Steady State Half-life (t1/2)
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Half-life (t1/2) was estimated using a non-compartmental method.
Time frame: Up to day 22
Steady State Apparent Oral Clearance (CL/F)
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Apparent oral clearance (CL/F) was estimated using a non-compartmental method.
Time frame: Up to day 22
Steady State Area Under the Plasma Concentration Time Curve (AUC)
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Area under the plasma concentration time curve (AUC) was estimated using a non-compartmental method.
Time frame: Up to day 22
Number of Subjects With Objective Responses
Objective responses included complete response (CR) and partial response (PR).
Time frame: Up to 2 years
Association Between Neutropenia and Single Dose Palbociclib AUC
Neutrophil count decreased adverse events observed in course 1 that were at least possibly attributable to palbociclib were included in analysis. Based on the highest toxicity grade reported, all participants, irrespective of their dose level or stratum, were combined and classified into three categories: 0 = no toxicity reported, 1 = grade 1 or 2, and 2 = grade 3 or 4. Association between neutrophil count decreased and single dose palbociclib AUC for all participants was examined.
Time frame: Up to approximately 4 weeks
Association Between Lymphopenia and Single Dose Palbociclib AUC
Lymphocyte count decreased adverse events observed in course 1 that were at least possibly attributable to palbociclib were included in analysis. Based on the highest toxicity grade reported, all participants, irrespective of their dose level or stratum, were combined and classified into three categories: 0 = no toxicity reported, 1 = grade 1 or 2, and 2 = grade 3 or 4. Association between Lymphocyte count decreased and single dose palbociclib AUC for all participants was examined.
Time frame: Up to approximately 4 weeks
Association Between Leukopenia and Single Dose Palbociclib AUC
White blood cell count decreased adverse events observed in course 1 that were at least possibly attributable to palbociclib were included in analysis. Based on the highest toxicity grade reported, all participants, irrespective of their dose level or stratum, were combined and classified into three categories: 0 = no toxicity reported, 1 = grade 1 or 2, and 2 = grade 3 or 4. Association between white blood cell count decreased and single dose palbociclib AUC for all participants was examined.
Time frame: Up to approximately 4 weeks
Number of Subjects With Cyclin-dependent Kinase-4 (CDK4) Copy Number Variations
CDK4 is a key component in signaling pathways inside normal cells and cancer cells. CDK4 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Time frame: At enrollment
Number of Subjects With Cyclin-dependent Kinase-6 (CDK6) Copy Number Variations
CDK6 is a key component in signaling pathways inside normal cells and cancer cells. CDK6 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Time frame: At enrollment
Number of Subjects With Cyclin D1 Copy Number Variations
Cyclin D1 is a key component in signaling pathways inside normal cells and cancer cells. Cyclin D1 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Time frame: At enrollment
Number of Subjects With Cyclin D2 Copy Number Variations
Cyclin D2 is a key component in signaling pathways inside normal cells and cancer cells. Cyclin D2 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Time frame: At enrollment
Number of Subjects With Cyclin D3 Copy Number Variations
Cyclin D3 is a key component in signaling pathways inside normal cells and cancer cells. Cyclin D3 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Time frame: At enrollment
Number of Subjects With Ink4a-ARF Loss Copy Number Variations
Ink4a-ARF is a key component in signaling pathways inside normal cells and cancer cells. Ink4a-ARF loss copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Time frame: At enrollment
Polymorphisms in Efflux-transporter Proteins P-glycoprotein (P-gp; ABCB1)
Polymorphisms in ABCB1 encode for efflux-transporter proteins P-glycoprotein (P-gp), for which palbociclib has been shown as a substrate. Genomic DNA was to be isolated from peripheral blood samples from consenting patients to determine ABCB1 polymorphisms.
Time frame: At enrollment
Polymorphisms in Breast Cancer Resistance Protein (BCRP; ABCG2)
Polymorphisms in ABCG2 encode for BCRP, for which palbociclib has been shown as a substrate. Genomic DNA was to be isolated from peripheral blood samples from consenting patients to determine ABCG2 polymorphisms.
Time frame: At enrollment
Patients between 4 and 21 years of age with histologically confirmed retinoblastoma protein (Rb1) positive, primary recurrent, progressive, or refractory central nervous system tumors were enrolled at Pediatric Brain Tumor Consortium member institutions. The first patient was enrolled on 12/8/2014 and the last patient was enrolled on 10/10/2018.
| Milestone | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Started | 3 | 12 | 6 | 4 | 10 |
| Completed | 3 | 10 | 5 | 4 | 8 |
| Not completed | 0 | 2 | 1 | 0 | 2 |
| Withdrew: Adverse event | 0 | 1 | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 0 | 1 |
| Withdrew: Not meet dose reduction bsa requirement | 0 | 1 | 0 | 0 | 0 |
Rolling-6 design was used to estimate MTD. The MTD was empirically defined as the highest dose level at which six patients were treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level had been determined to be too toxic. Stratum I consisted of less-heavily pre-treated patients.
| mg/m2/day | Stratum I |
|---|---|
| Maximum Tolerated Dose (MTD) of Palbociclib in Stratum I | 75 |
Rolling-6 design was used to estimate MTD. The MTD was empirically defined as the highest dose level at which six patients were treated with at most one patient experiencing a DLT and the next higher dose level had been determined to be too toxic. Stratum II consisted of heavily pre-treated patients.
| mg/m2/day | Stratum II |
|---|---|
| Maximum Tolerated Dose (MTD) of Palbociclib in Stratum II | 75 |
DLTs were defined as any of the following adverse events that were at least possibly related to palbociclib that occurred during the first 4 weeks of therapy regardless of expectedness. Hematologic DLTs included grade 3 neutropenia with fever and sepsis, grade 3 thrombocytopenia and/or requiring a platelet transfusion on 2 separate days within a 7-day period, or any grade 4 hematologic toxicity except lymphopenia. Non-hematologic DLTs included any grade 4 non-hematologic toxicity, any grade 3 non-hematologic toxicity with some exceptions (e.g., nausea and vomiting of \< 5 days; diarrhea and/or electrolyte disturbances which have not been maximally treated; AST/ALT elevation that returns to levels meeting eligibility criteria within 7 days of study drug interruption and does not recur upon restarting drug), or any grade 2 non-hematologic toxicity that persists for \> 7 days and is considered medically significant or sufficiently intolerable by patients requires treatment interruption.
| Participants | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Number of Patients Who Experienced Dose Limiting Toxicities (DLTs) | 0 | 2 | 2 | 0 | 1 |
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Apparent volume of central compartment (Vc/F) was estimated using a non-compartmental method.
| L/m^2 | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Single Dose Apparent Volume of Central Compartment (Vc/F) | 672 (622 to 1189) | 741 (562 to 1856) | 708 (601 to 819) | 847 (373 to 1153) | 850 (398 to 3653) |
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Elimination rate constant (Ke) was estimated using a non-compartmental method.
| per hour | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Single Dose Elimination Rate Constant (Ke) | 0.053 (0.045 to 0.055) | 0.053 (0.030 to 0.070) | 0.048 (0.023 to 0.083) | 0.051 (0.031 to 0.070) | 0.051 (0.014 to 0.097) |
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Half-life (t1/2) was estimated using a non-compartmental method.
| hour | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Single Dose Half-life (t1/2) | 13.0 (12.5 to 15.5) | 13.0 (9.9 to 22.8) | 14.6 (8.4 to 29.8) | 13.8 (10.0 to 22.0) | 13.5 (7.1 to 48.7) |
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Apparent oral clearance (CL/F) was estimated using a non-compartmental method.
| L/h/m^2 | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Single Dose Apparent Oral Clearance (CL/F) | 35.8 (34.4 to 53.1) | 38.4 (29.3 to 72.0) | 33.7 (17.3 to 63.3) | 37.2 (16.9 to 64.3) | 24.4 (11.7 to 355.0) |
On day 1 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 0.5, 1, 2, 4, 8 (±1), 10 (±0.5) optional, 24 (±4), 48 (±4) hours after the oral dose of palbociclib. Area under the plasma concentration time curve (AUC) was estimated using a non-compartmental method.
| h*ng/mL | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Single Dose Area Under the Plasma Concentration Time Curve (AUC) | 1156 (810 to 1164) | 1743 (892 to 2537) | 2407 (1485 to 3252) | 1289 (747 to 2834) | 2538 (189 to 2951) |
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Apparent volume of central compartment (Vc/F) was estimated using a non-compartmental method.
| L/m^2 | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Steady State Apparent Volume of Central Compartment (Vc/F) | 491 (465 to 517) | 449 (282 to 1560) | 442 (383 to 501) | 705 (250 to 1308) | 458 (247 to 919) |
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Elimination rate constant (Ke) was estimated using a non-compartmental method.
| per hour | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Steady State Elimination Rate Constant (Ke) | 0.052 (0.041 to 0.066) | 0.050 (0.017 to 0.110) | 0.062 (0.054 to 0.071) | 0.032 (0.024 to 0.049) | 0.039 (0.032 to 0.074) |
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Half-life (t1/2) was estimated using a non-compartmental method.
| hour | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Steady State Half-life (t1/2) | 13.7 (10.5 to 16.9) | 13.7 (6.5 to 41.6) | 11.3 (9.8 to 12.8) | 23.1 (14.2 to 29.4) | 17.9 (9.4 to 21.4) |
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Apparent oral clearance (CL/F) was estimated using a non-compartmental method.
| L/h/m^2 | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Steady State Apparent Oral Clearance (CL/F) | 26.6 (19.0 to 34.2) | 25.8 (12.3 to 101.0) | 28.1 (20.8 to 35.3) | 17.0 (9.7 to 64.0) | 16.1 (12.1 to 62.4) |
On day 21 of course 1, series blood samples for palbociclib pharmacokinetic studies were collected at pre-dose, 1, 2, 4, 8 (±1), 10 (±0.5) optional, and 24 (±4) hours after the dose. Area under the plasma concentration time curve (AUC) was estimated using a non-compartmental method.
| h*ng/mL | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Steady State Area Under the Plasma Concentration Time Curve (AUC) | 1211 (972 to 1450) | 2143 (521 to 4070) | 2193 (1520 to 3168) | 1410 (559 to 3301) | 2359 (952 to 4253) |
Objective responses included complete response (CR) and partial response (PR).
| Participants | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Number of Subjects With Objective Responses | 0 | 0 | 0 | 0 | 0 |
Neutrophil count decreased adverse events observed in course 1 that were at least possibly attributable to palbociclib were included in analysis. Based on the highest toxicity grade reported, all participants, irrespective of their dose level or stratum, were combined and classified into three categories: 0 = no toxicity reported, 1 = grade 1 or 2, and 2 = grade 3 or 4. Association between neutrophil count decreased and single dose palbociclib AUC for all participants was examined.
| h*ng/mL | All Patients |
|---|---|
| No neutropenia | 1424.4 ± 966.3 |
| Grade 1 or 2 neutropenia | 2166.3 ± 797.8 |
| Grade 3 or 4 neutropenia | 1937.6 ± 621.8 |
Lymphocyte count decreased adverse events observed in course 1 that were at least possibly attributable to palbociclib were included in analysis. Based on the highest toxicity grade reported, all participants, irrespective of their dose level or stratum, were combined and classified into three categories: 0 = no toxicity reported, 1 = grade 1 or 2, and 2 = grade 3 or 4. Association between Lymphocyte count decreased and single dose palbociclib AUC for all participants was examined.
| h*ng/mL | All Patients |
|---|---|
| No lymphopenia | 1727.5 ± 882.6 |
| Grade 1 or 2 lymphopenia | 1837.9 ± 592.7 |
| Grade 3 or 4 lymphopenia | 2159.0 ± 793.7 |
White blood cell count decreased adverse events observed in course 1 that were at least possibly attributable to palbociclib were included in analysis. Based on the highest toxicity grade reported, all participants, irrespective of their dose level or stratum, were combined and classified into three categories: 0 = no toxicity reported, 1 = grade 1 or 2, and 2 = grade 3 or 4. Association between white blood cell count decreased and single dose palbociclib AUC for all participants was examined.
| h*ng/mL | All Patients |
|---|---|
| No leukopenia | 1420.3 ± 955.1 |
| Grade 1 or 2 leukopenia | 1879.6 ± 682.6 |
| Grade 3 or 4 leukopenia | 2171.6 ± 712.9 |
CDK4 is a key component in signaling pathways inside normal cells and cancer cells. CDK4 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Results for this outcome have not been posted.
CDK6 is a key component in signaling pathways inside normal cells and cancer cells. CDK6 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Results for this outcome have not been posted.
Cyclin D1 is a key component in signaling pathways inside normal cells and cancer cells. Cyclin D1 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Results for this outcome have not been posted.
Cyclin D2 is a key component in signaling pathways inside normal cells and cancer cells. Cyclin D2 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Results for this outcome have not been posted.
Cyclin D3 is a key component in signaling pathways inside normal cells and cancer cells. Cyclin D3 copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Results for this outcome have not been posted.
Ink4a-ARF is a key component in signaling pathways inside normal cells and cancer cells. Ink4a-ARF loss copy number variations were to be assessed by array comparative genomic hybridization in available tumor tissues from consenting patients.
Results for this outcome have not been posted.
Polymorphisms in ABCB1 encode for efflux-transporter proteins P-glycoprotein (P-gp), for which palbociclib has been shown as a substrate. Genomic DNA was to be isolated from peripheral blood samples from consenting patients to determine ABCB1 polymorphisms.
Results for this outcome have not been posted.
Polymorphisms in ABCG2 encode for BCRP, for which palbociclib has been shown as a substrate. Genomic DNA was to be isolated from peripheral blood samples from consenting patients to determine ABCG2 polymorphisms.
Results for this outcome have not been posted.
Collected over Up to 2 years after starting treatment. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stratum I, Dose Level 1 (50 mg/m2) | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Stratum I, Dose Level 2 (75 mg/m2) | 3/12 (25%) | 1/12 (8.3%) | 12/12 (100%) |
| Stratum I, Dose Level 3 (95 mg/m2) | 1/6 (16.7%) | 1/6 (16.7%) | 5/6 (83.3%) |
| Stratum II, Dose Level 1 (50 mg/m2) | 1/4 (25%) | 0/4 (0%) | 4/4 (100%) |
| Stratum II, Dose Level 2 (75mg/m2) | 1/9 (11.1%) | 0/9 (0%) | 9/9 (100%) |
| Event | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| Neutrophil count decreasedInvestigations | 0/3 | 0/12 | 1/6 | 0/4 | 0/9 |
| DehydrationMetabolism and nutrition disorders | 0/3 | 1/12 | 0/6 | 0/4 | 0/9 |
| Event | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) |
|---|---|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 0/3 | 5/12 | 2/6 | 4/4 | 6/9 |
| Neutrophil count decreasedInvestigations | 1/3 | 10/12 | 3/6 | 4/4 | 7/9 |
| White blood cell decreasedInvestigations | 2/3 | 10/12 | 5/6 | 4/4 | 7/9 |
| AnorexiaMetabolism and nutrition disorders | 1/3 | 1/12 | 0/6 | 3/4 | 0/9 |
| Lymphocyte count decreasedInvestigations | 2/3 | 8/12 | 3/6 | 2/4 | 4/9 |
| HyperglycemiaMetabolism and nutrition disorders | 2/3 | 0/12 | 0/6 | 0/4 | 0/9 |
| Platelet count decreasedInvestigations | 1/3 | 6/12 | 3/6 | 2/4 | 5/9 |
| FatigueGeneral disorders | 1/3 | 5/12 | 1/6 | 1/4 | 3/9 |
| ConstipationGastrointestinal disorders | 1/3 | 4/12 | 1/6 | 1/4 | 1/9 |
| DiarrheaGastrointestinal disorders | 1/3 | 2/12 | 0/6 | 1/4 | 0/9 |
Summary statistics for baseline characteristics are shown for all enrolled patients (n = 35).
| Age, Continuous(years) | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) | Total |
|---|---|---|---|---|---|---|
| Median | 16.6 (9.7 to 16.6) | 12.6 (7.0 to 21.1) | 9.3 (4.9 to 19.3) | 16.5 (13.3 to 17.2) | 10.5 (6.3 to 21.6) | 12.7 (4.9 to 21.6) |
| Sex: Female, Male(Participants) | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) | Total |
|---|---|---|---|---|---|---|
| Female | 1 | 5 | 3 | 0 | 3 | 12 |
| Male | 2 | 7 | 3 | 4 | 7 | 23 |
| Ethnicity (NIH/OMB)(Participants) | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) | Total |
|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 3 | 2 | 0 | 3 | 8 |
| Not Hispanic or Latino | 3 | 6 | 4 | 2 | 5 | 20 |
| Unknown or Not Reported | 0 | 3 | 0 | 2 | 2 | 7 |
| Race (NIH/OMB)(Participants) | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | 0 | 1 |
| Asian | 1 | 1 | 1 | 0 | 0 | 3 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 2 | 0 | 0 | 2 | 4 |
| White | 2 | 7 | 4 | 3 | 7 | 23 |
| More than one race | 0 | 0 | 1 | 0 | 0 | 1 |
| Unknown or Not Reported | 0 | 2 | 0 | 0 | 1 | 3 |
| Region of Enrollment(participants) | Stratum I, Dose Level 1 (50 mg/m2) | Stratum I, Dose Level 2 (75 mg/m2) | Stratum I, Dose Level 3 (95 mg/m2) | Stratum II, Dose Level 1 (50 mg/m2) | Stratum II, Dose Level 2 (75mg/m2) | Total |
|---|---|---|---|---|---|---|
| United States | 3 | 12 | 6 | 4 | 10 | 35 |
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Studies of the drug tested here: Palbociclib
Pediatric Brain Tumor Consortium