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: 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: 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: 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) 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), 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: 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: 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
šøš°Banska Bystrica, Slovakia
University of Alabama at Birmingham/Children's of Alabama
šŗšøBirmingham, Alabama, United States
Phoenix Children's Hospital
šŗšøPhoenix, Arizona, United States
MemorialCare Health System - Long Beach Medical Center
šŗšøLong Beach, California, United States
Children's Hospital Los Angeles
šŗšøLos Angeles, California, United States
Children's Hospital and Research Center at Oakland
šŗšøOakland, California, United States
Children's Hospital of Orange County
šŗšøOrange, California, United States
Lucile Packard Children's Hospital
šŗšøPalo Alto, California, United States
UCSF Medical Center
šŗšøSan Francisco, California, United States
University of California San Francisco,
šŗšøSan Francisco, California, United States
Children's Hospital Colorado
šŗšøAurora, Colorado, United States
Children's National Hospital
šŗšøWashington, District of Columbia, United States
UF Health Shands Hospital
šŗšøGainesville, Florida, United States
University of Florida College of Medicine
šŗšøGainesville, Florida, United States
Johns Hopkins All Children's Hospital
šŗšøTampa, Florida, United States
Johns Hopkins All Children's Outpatient Care Center
šŗšøSaint Petersburg, Florida, United States
Children's Healthcare of Atlanta at Egleston
šŗšøAtlanta, Georgia, United States
Children's Healthcare of Atlanta at Scottish Rite
šŗšøAtlanta, Georgia, United States
Children's Healthcare of Atlanta, Medical Office Building
šŗšøAtlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
šŗšøChicago, Illinois, United States
Indiana University
šŗšøIndianapolis, Indiana, United States
Norton Children's Hospital
šŗšøLouisville, Kentucky, United States
Novak Center for Children's Health
šŗšøLouisville, Kentucky, United States
Johns Hopkins University
šŗšøBaltimore, Maryland, United States
University of Michigan Health System
šŗšøAnn Arbor, Michigan, United States
University of Minnesota Masonic Children's Hospital
šŗšøMinneapolis, Minnesota, United States
University of Minnesota Medical Center, Fairview
šŗšøMinneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
šŗšøMinneapolis, Minnesota, United States
University of Minnesota
šŗšøMinneapolis, Minnesota, United States
University of Mississippi Medical Center
šŗšøJackson, Mississippi, United States
Children's Mercy Hospital
šŗšøKansas City, Missouri, United States
Washington University School of Medicine
šŗšøSaint Louis, Missouri, United States
Robert Wood Johnson University Hospital
šŗšøNew Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey
šŗšøNew Brunswick, New Jersey, United States
Montefiore Medical Center
šŗšøBronx, New York, United States
John R. Oishei Childrens Hospital
šŗšøBuffalo, New York, United States
Roswell Park Cancer Institute
šŗšøBuffalo, New York, United States
Cohen Children's Medical Center
šŗšøNew Hyde Park, New York, United States
Morgan Stanley Children's Hospital of New York-Presbyetrian Hospital
šŗšøNew York, New York, United States
Cincinnati Children's Hospital Medical Center
šŗšøCincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
šŗšøCleveland, Ohio, United States
Nationwide Children's Hospital
šŗšøColumbus, Ohio, United States
Cincinnati Children's Liberty Campus
šŗšøLiberty Township, Ohio, United States
University of Oklahoma Health Sciences Center
šŗšøOklahoma City, Oklahoma, United States
Oregon Health & Science University
šŗšøPortland, Oregon, United States
Penn State Children's Hospital and Penn State Health Milton S. Hershey Medical Center
šŗšøHershey, Pennsylvania, United States
Buerger Center for Advanced Pediatric Care
šŗšøPhiladelphia, Pennsylvania, United States
Children's Hospital of Philadelphia
šŗšøPhiladelphia, Pennsylvania, United States
UPMC Children's Hospital of Pittsburgh
šŗšøPittsburgh, Pennsylvania, United States
Children's Blood and Cancer Center
šŗšøAustin, Texas, United States
Dell Children's Medical Center
šŗšøAustin, Texas, United States
Children's Medical Center Dallas
šŗšøDallas, Texas, United States
Cook Children's Medical Center
šŗšøFort Worth, Texas, United States
Cook Children's H/O Infusion Center
šŗšøGrapevine, Texas, United States
Texas Children's Hospital
šŗšøHouston, Texas, United States
Children's Medical Center Plano
šŗšøPlano, Texas, United States
Intermountain - Primary Children's Hospital
šŗšøSalt Lake City, Utah, United States
Primary Children's Hospital Outpatient Services
šŗšøSalt Lake City, Utah, United States
Children's Hospital of The King's Daughters
šŗšøNorfolk, Virginia, United States
Children's Hospital of Richmond at VCU
šŗšøRichmond, Virginia, United States
Seattle Children's Hospital
šŗšøSeattle, Washington, United States
Children's Wisconsin
šŗšøMilwaukee, Wisconsin, United States
Medical College of Wisconsin
šŗšøMilwaukee, Wisconsin, United States
Hospital Pequeno Principe / A ssociacao Hospitalar de Protecao a Infancia
š§š·Curitiba, ParanĆ”, Brazil
Hospital Pequeno PrĆncipe
š§š·Curitiba, ParanĆ”, Brazil
Hospital de Clinicas de Porto Alegre
š§š·Porto Alegre, RIO Grande DO SUL, Brazil
FundaĆ§Ć£o Pio XII - Hospital de CĆ¢ncer de Barretos
š§š·Barretos, SĆO Paulo, Brazil
Instituto Nacional de CĆ¢ncer - INCA
š§š·Rio de Janeiro, Brazil
Hospital Santa Marcelina
š§š·SĆ£o Paulo, Brazil
Alberta Children's Hospital
šØš¦Calgary, Alberta, Canada
Stollery Children's Hospital
šØš¦Edmonton, Alberta, Canada
The Hospital for Sick Children
šØš¦Toronto, Ontario, Canada
CHU Sainte-Justine
šØš¦Montreal, Quebec, Canada
Detska nemocnice FN Brno
šØšæBrno, Brno-mÄsto, Czechia
Fakultni nemocnice v Motole
šØšæPraha, Praha 5, Czechia
Institut BergoniƩ - Centre RƩgional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
š«š·Bordeaux, Aquitaine, France
Centre Leon Berard
š«š·Lyon, RhĆ“ne-alpes, France
Gustave Roussy
š«š·Villejuif, Val-de-marne, France
Assistance Publique HĆ“pitaux de Marseille - HĆ“pital de la Timone
š«š·Marseille, France
UniversitƤtsklinikum Essen
š©šŖEssen, Nordrhein-westfalen, Germany
All India Institute of Medical Sciences
š®š³New Delhi, Delhi, India
Rajiv Gandhi Cancer Institute And Research Centre
š®š³New Delhi, Delhi, India
Artemis hospital
š®š³Gurugram, Haryana, India
National Cancer Center
š°š·Goyang-si, KyĒnggi-do, Korea, Republic of
Seoul National University Hospital
š°š·Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Asan Medical Center
š°š·Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Samsung Medical Center
š°š·Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Instytut Matki i Dziecka
šµš±Warsaw, Mazowieckie, Poland
Narodny ustav detskych chorob
šøš°Bratislava, Slovakia
Hospital Universitari Vall d'Hebron
šŖšøBarcelona, Barcelona [barcelona], Spain
Hospital Infantil Universitario NiƱo JesĆŗs
šŖšøMadrid, Madrid, Comunidad DE, Spain
Sahlgrenska Universitetssjukhuset Ćstra
šøšŖGothenburg, VƤstra Gƶtalands LĆN [se-14], Sweden
Ege Universitesi Hastanesi
š¹š·Ä°zmir, Ä°Ģzmir, Turkey
Hacettepe Universite Hastaneleri
š¹š·Ankara, Turkey
Royal Victoria Infirmary
š¬š§Newcastle upon Tyne, England, United Kingdom
Royal Hospital for Children
š¬š§Glasgow, Scotland, United Kingdom
Leeds General Infirmary
š¬š§Leeds, United Kingdom
University College London Hospital, NHS Foundation Trust
š¬š§London, United Kingdom