Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
- Conditions
- Rhabdoid TumorSolid TumorsMedulloblastomaEwing SarcomaRhabdomyosarcomaDiffuse Intrinsic Pontine GliomaNeuroblastoma
- Interventions
- Registration Number
- NCT03709680
- Lead Sponsor
- Pfizer
- Brief Summary
A study to learn about safety and find out maximum tolerable dose of palbociclib given in combination with chemotherapy (temozolomide with irinotecan or topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumors (phase 1). Neuroblastoma tumor specific cohort to further evaluate antitumor activity of palbociclib in combination with topotecan and cyclophosphamide in children, adolescents, and young adults with recurrent or refractory neuroblastoma. Phase 2 to learn about the efficacy of palbociclib in combination with irinotecan and temozolomide when compared with irinotecan and temozolomide alone in the treatment of children, adolescents, and young adults with recurrent or refractory Ewing sarcoma (EWS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 128
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 2 Arm A Palbociclib Palbociclib in combination with irinotecan and temozolomide. Phase 1 Temozolomide Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide. Phase 2 Arm B Temozolomide Irinotecan and temozolomide alone. Phase 1 Tumor specific cohort - Neuroblastoma Palbociclib Palbociclib in combination with topotecan and cyclophosphamide. Phase 1 Tumor specific cohort - Neuroblastoma Cyclophosphamide Palbociclib in combination with topotecan and cyclophosphamide. Phase 2 Arm A Irinotecan Palbociclib in combination with irinotecan and temozolomide. Phase 2 Arm A Temozolomide Palbociclib in combination with irinotecan and temozolomide. Phase 1 Palbociclib Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide. Phase 1 Irinotecan Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide. Phase 1 Topotecan Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide. Phase 1 Cyclophosphamide Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide. Phase 2 Arm B Irinotecan Irinotecan and temozolomide alone. Phase 1 Tumor specific cohort - Neuroblastoma Topotecan Palbociclib in combination with topotecan and cyclophosphamide.
- Primary Outcome Measures
Name Time Method Phase 1: Dose Expansion Parts: Frequency of adverse events At least 28 days after last dose For Dose Expansion and Tumor-Specific Expansion Parts: Adverse events to be reported during treatment and for at least 28 days after last dose.
Phase 2 open-label, randomized: Event-free survival (EFS) based on Investigator assessment. Baseline to Month 24. EFS is defined as the time from randomization until first event (ie, progression, recurrence following response, second malignancy or death without progression or recurrence).
Phase 1: First Cycle Dose-Limiting Toxicities (DLT) First cycle (cycle length is approximately 21 days) For Dose Escalation/Determination Part: DLT defined as any of the following events occurring during the first treatment cycle and considered at least possibly-related to study medication:Grade 4 neutropenia lasting greater than 7 days;Grade 4 thrombocytopenia lasting greater than 7 days or need for platelet transfusion for a platelet count of \< 20,000 per cubic millimeters twice within a 7-day period;greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia;Grade 3 or greater non-hematologic toxicities despite optimal treatment;any Grade 2 or greater non-hematologic toxicity requiring discontinuation or interruption of palbociclib for 7 or more consecutive days during the first cycle or any grade non-hematologic toxicity that delays the start of Cycle 2 by more than 14 days;clinically significant non-hematologic laboratory test abnormality Grade 3 or greater not resolving to Grade 1 or baseline within 7 days.
Phase 1: Dose Expansion Parts: Percentage of Participants With Complete Response or Partial Response Through the end of treatment (up to at least 28 days after last dose) For Dose Expansion and Tumor-Specific Expansion Parts: patients with confirmed Complete Response or Partial Response per Response Evaluation Criteria in Solid Tumors (RECIST, v.1.1) or modified Response Assessment in Neuro-Oncology (RANO) for central nervous system malignancies, or International Neuroblastoma Response Criteria (INRC) for neuroblastoma, during study treatment, assessed approximately every 2 to 4 cycles (each cycle is approximately 21 days).
- Secondary Outcome Measures
Name Time Method Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Maximum plasma concentration time (Tmax) PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Frequency of adverse events At least 28 days after last dose Adverse events to be reported during treatment and for at least 28 days after last dose.
Phase 2 open-label, randomized: Event-free survival (EFS) assessed by an independent review committee. Baseline to Month 24. EFS is defined as the time from randomization until first event (ie, progression, recurrence following response, second malignancy or death without progression or recurrence).
Phase 1 and Phase 2:Palbociclib Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max) PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Percentage of participants with laboratory abnormalities At least 28 days after last dose Magnesium, Calcium, Creatinine, Albumin, Alanine aminotransferase, Aspartate aminotransferase, Glucose, Phosphorus, Total Bilirubin, Blood urea nitrogen, Alkaline phosphatase, Sodium, Potassium, Chloride, Platelet Count, White Blood Cell Count (differential), hemoglobin, INR or prothrombin Time, HbA1c
Phase 1 and Phase 2: Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings At least 28 days after last dose Clinically significant ECG findings included: corrected QT (QTc) \> 450 ms, QTc \>500 ms, change in QTc between 30 and 60 ms, change in QTc greater than or equal to 60 ms.
Phase 1 and Phase 2: Percentage of Participants With Complete Response or Partial Response Through the end of treatment (up to at least 28 days after last dose) Patients with confirmed Complete Response or Partial Response per Response Evaluation Criteria in Solid Tumors (RECIST, v.1.1) or modified Response Assessment in Neuro-Oncology (RANO) for central nervous system malignancies, or International Neuroblastoma Response Criteria (INRC) for neuroblastoma, during study treatment, assessed approximately every 2 to 4 cycles (each cycle is approximately 21 days).
Phase 1 and Phase 2: Progression Free Survival (PFS) Up to 2 years PFS defined as time from date of enrollment to earliest date of the death or progressive disease
Phase 2 : comparison of PET-CT response assessment to objective response on CT/MRI. up to completion of Cycle 4 ( 12 weeks of therapy) PET-CT response assessment will be compared to objective response on MRI/CT, as data permit.
Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t) PK sampling at time points during Cycle 1 (day 2,5, 6,14) and Cycle 2 (day 5 and 14). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Oral plasma clearance (CL/F) PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max) PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs At least 28 days after last dose systolic and diastolic blood pressure, pulse
Phase 1 and Phase 2: Duration of response (DoR) for Participants Who Achieved Complete Response or Partial Response Up to 2 years DoR defined as time from date of first response (Complete Response or Partial Response) in responders to date of progression or death
Phase 1 and Phase 2: Overall Survival (OS) Up to 2 years OS defined as the time from enrollment to date of death due to any cause.
Phase 2: the impact of the combination of palbociclib with TMZ and IRN treatment on the quality of life (QoL) of patients with refractory or recurrent EWS. Up to Cycle 5 (completion of 12 weeks of treatment) Results of QoL reported by patient at baseline and after 2 and 4 cycles using age-appropriate PROMIS tools will be summarized for both treatment arms, as data permit.
Days of hospitalization will be compared in both treatment arms.Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t) PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum plasma concentration time (Tmax) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Topotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Cyclophosphamide Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Palbociclib Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough) PK sampling at time points during Cycle 1 (day 2, 5, 6, 14) and Cycle 2 (day 5 and 14). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough) PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Cyclophosphamide Pharmacokinetics, Oral plasma clearance (CL/F) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Cyclophosphamide Pharmacokinetics, Maximum plasma concentration time (Tmax) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Maximum plasma concentration time (Tmax) PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Temozolomide Pharmacokinetics, Oral plasma clearance (CL/F) PK sampling at time points during Cycle 1 (day 5) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Irinotecan (and active metabolites), Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Cyclophosphamide Pharmacokinetics, Measured concentration at the end of a dosing interval at steady state (taken directly before next administration) (Css,trough) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Oral plasma clearance (CL/F) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Topotecan (and active metabolites) Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1 and Phase 2: Irinotecan (and active metabolites) Pharmacokinetics, Maximum observed plasma concentration during a dosing interval at steady state (Css, max) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Phase 1: Cyclophosphamide Pharmacokinetics, Area under the concentration-time curve during a dosing interval at steady state (AUCss,t) PK sampling at time points during Cycle 1 (day 2, 5 and 6) and Cycle 2 (day 5). Each cycle is 21 days. Multiple Dose (assuming steady state is achieved), as data permit
Trial Locations
- Locations (98)
Detska fakultna nemocnica s poliklinikou Banska Bystrica
🇸🇰Banska Bystrica, Slovakia
University of Alabama at Birmingham/Children's of Alabama
🇺🇸Birmingham, Alabama, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
MemorialCare Health System - Long Beach Medical Center
🇺🇸Long Beach, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital and Research Center at Oakland
🇺🇸Oakland, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Lucile Packard Children's Hospital
🇺🇸Palo Alto, California, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
University of California San Francisco,
🇺🇸San Francisco, California, United States
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