Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
PHASE 1/2 STUDY TO EVALUATE PALBOCICLIB (IBRANCE®) IN COMBINATION WITH IRINOTECAN AND TEMOZOLOMIDE OR IN COMBINATION WITH TOPOTECAN AND CYCLOPHOSPHAMIDE IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS
2 other identifiers
interventional
128
14 countries
101
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2019
Longer than P75 for phase_2
101 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 9, 2018
CompletedFirst Posted
Study publicly available on registry
October 17, 2018
CompletedStudy Start
First participant enrolled
May 24, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 26, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
October 18, 2025
CompletedJanuary 14, 2025
January 1, 2025
5.3 years
October 9, 2018
January 13, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Phase 2 open-label, randomized: Event-free survival (EFS) based on Investigator assessment.
EFS is defined as the time from randomization until first event (ie, progression, recurrence following response, second malignancy or death without progression or recurrence).
Baseline to Month 24.
Phase 1: First Cycle Dose-Limiting Toxicities (DLT)
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.
First cycle (cycle length is approximately 21 days)
Phase 1: Dose Expansion Parts: Frequency of adverse events
For Dose Expansion and Tumor-Specific Expansion Parts: Adverse events to be reported during treatment and for at least 28 days after last dose.
At least 28 days after last dose
Phase 1: Dose Expansion Parts: Percentage of Participants With Complete Response or Partial Response
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).
Through the end of treatment (up to at least 28 days after last dose)
Secondary Outcomes (36)
Phase 1 and Phase 2: Frequency of adverse events
At least 28 days after last dose
Phase 1 and Phase 2: Percentage of participants with laboratory abnormalities
At least 28 days after last dose
Phase 1 and Phase 2: Number of Participants With Clinically Significant Treatment-emergent Electrocardiogram (ECG) Findings
At least 28 days after last dose
Phase 1 and Phase 2: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
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.
- +31 more secondary outcomes
Study Arms (4)
Phase 2 Arm A
EXPERIMENTALPalbociclib in combination with irinotecan and temozolomide.
Phase 1
EXPERIMENTALPalbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
Phase 2 Arm B
ACTIVE COMPARATORIrinotecan and temozolomide alone.
Phase 1 Tumor specific cohort - Neuroblastoma
EXPERIMENTALPalbociclib in combination with topotecan and cyclophosphamide.
Interventions
Phase 1: Administered (oral) at 55 mg/m2, 75 mg/m2, or 40 mg/m2, or 95 mg/m2 or 115 mg/m2 on days 1-14 of a 21-day cycle Phase 1 Tumor specific cohort-Neuroblastoma and Phase 2 : Administered (oral) at 75 mg/m2 on days 1-14 of a 21-day cycle
Phase 1 and Phase 2: Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
Phase 1 and Phase 2: Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Phase 1 only : Administered at 0.75 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Phase 1 only: Administered at 250 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Eligibility Criteria
You may qualify if:
- Histologically confirmed relapsed or refractory solid tumor as follows:
- For dose escalation and dose determination parts: Histologically confirmed relapsed or refractory solid tumor (including CNS tumors but not lymphomas). Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll.
- For dose expansion and tumor specific cohorts: Histologically confirmed relapsed or refractory solid tumor including but not limited to EWS, rhabdoid tumor, rhabdomyosarcoma, neuroblastoma, and medulloblastoma. Patients with Diffuse Intrinsic Pontine Glioma do not require histological only radiographic confirmed relapse to enroll. EWS is not eligible for TOPO and CTX tumor-specific cohorts.
- For randomized Phase 2 part: Histologically confirmed Ewing sarcoma at diagnosis or at relapse, with presence of EWSR1-ETS or FUS-ETS rearrangement. Histopathology confirmation of both EWSR1-ETS or FUS-ETS rearrangement partners is required OR availability of formalin fixed paraffin embedded (FFPE) tumor tissue sample for central testing. Patient must have relapsed or have refractory disease and at least evaluable disease in at least one site other than bone marrow that can be followed by imaging.
- Age ≥2 and \<21 years at the time of study entry.
- Lansky performance status ≥50% for patients ≤16 years of age, or Eastern Cooperative Oncology Group (ECOG) 0, 1 or 2 for patients \>16 years of age.
- Adequate bone marrow function.
- Absolute neutrophil count ≥1000/mm3;
- Platelet count ≥75,000/mm3 (transfusion independent, no platelet transfusion in past 7 days prior study entry);
- Hemoglobin ≥8.5 g/dL (transfusion allowed).
- Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
- Adequate liver function, including:
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
- ≤2.5 × upper limit of normal (ULN) or ≤5 × ULN for age, if attributable to disease involvement of the liver;
- Total bilirubin ≤1.5 × ULN for age, unless the patient has documented Gilbert's syndrome.Patients with documented Gilbert's syndrome are eligible if direct bilirubin is within normal ranges (≤ULN).
- +10 more criteria
You may not qualify if:
- Phase 1 and tumor specific cohorts: For palbociclib with IRN and TMZ combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing regimen that includes TMZ. Patients who have received the combination of IRN and TMZ and did not progress while on these medications are eligible. For patients enrolling in the palbociclib with TOPO and CTX combination, prior treatment with a CDK4/6 inhibitor or progression while on treatment with a TOPO-containing regimen that includes CTX. Patients who have received the combination of TOPO and CTX and did not progress while on these medications are eligible. Phase 2 portion: prior treatment with a CDK4/6 inhibitor or progression while on treatment with an IRN-containing or TMZ-containing regimen. Patients who have received IRN and/or TMZ and did not progress while on these medications are eligible.
- Prior intolerability to IRN and/or TMZ plus/minus palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for TOPO and CTX combination. For patients enrolled in the UK, any contraindication for IRN and/or TMZ treatment, as per the local SmPC.
- Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers within 12 days of study entry. Patients who are receiving strong uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1) inhibitors within 12 days of Cycle 1 Day 1 (C1D1) are not eligible for the palbociclib with IRN and TMZ combination. Patients who are receiving strong UGT1A1 inhibitors within 12 days of C1D1 are eligible for the palbociclib with TOPO and CTX combination (See Section 5.7.1 for list of products.)
- Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
- Prior irradiation to \>50% of the bone marrow (see Appendix 9).
- Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
- Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
- For IRN and TMZ with/without palbociclib combinations: known or suspected hypersensitivity to palbociclib, dacarbazine, IRN and/or TMZ. For combination of palbociclib with TOPO and CTX: known or suspected hypersensitivity to palbociclib, TOPO and/or CTX.
- Patients with known symptomatic brain tumors or brain metastases and require steroids, unless they have been on a stable or on a decreasing steroid dose for \>14 days.
- Patients with previously diagnosed brain metastases are eligible if they have completed their prior treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry for these metastases for at least 14 days post radiation and 4 weeks post-surgery and are neurologically stable.
- Hereditary bone marrow failure disorder.
- QTc \>470 msec.
- History of clinically significant or uncontrolled cardiac disease, including:
- History of or active congestive heart failure; if patient had congestive heart failure resolve and \>1 year from resolution, patient will be considered eligible;
- Clinically significant ventricular arrhythmia (such as ventricular tachycardia, ventricular fibrillation or Torsades de Pointes);
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
- Children's Oncology Groupcollaborator
Study Sites (101)
University of Alabama at Birmingham/Children's of Alabama
Birmingham, Alabama, 35233, United States
Phoenix Children's Hospital
Phoenix, Arizona, 85016, United States
MemorialCare Health System - Long Beach Medical Center
Long Beach, California, 90806, United States
Children's Hospital Los Angeles
Los Angeles, California, 90027, United States
Children's Hospital and Research Center at Oakland
Oakland, California, 94609, United States
Children's Hospital of Orange County
Orange, California, 92868, United States
Lucile Packard Children's Hospital
Palo Alto, California, 94304, United States
UCSF Medical Center
San Francisco, California, 94158, United States
University of California San Francisco,
San Francisco, California, 94158, United States
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
Children's National Hospital
Washington D.C., District of Columbia, 20010, United States
UF Health Shands Hospital
Gainesville, Florida, 32610, United States
University of Florida College of Medicine
Gainesville, Florida, 32610, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, 33701, United States
Johns Hopkins All Children's Outpatient Care Center
St. Petersburg, Florida, 33701, United States
Johns Hopkins All Children's Hospital
Tampa, Florida, 33612, United States
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, 30322, United States
Children's Healthcare of Atlanta at Scottish Rite
Atlanta, Georgia, 30342, United States
Children's Healthcare of Atlanta, Medical Office Building
Atlanta, Georgia, 30342, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Norton Children's Hospital
Louisville, Kentucky, 40202, United States
Novak Center for Children's Health
Louisville, Kentucky, 40202, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
University of Michigan Health System
Ann Arbor, Michigan, 48109, United States
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, 55454, United States
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, 55455, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Children's Mercy Hospital
Kansas City, Missouri, 64108, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08901, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903, United States
John R. Oishei Childrens Hospital
Buffalo, New York, 14203, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Cohen Children's Medical Center
New Hyde Park, New York, 11040, United States
Morgan Stanley Children's Hospital of New York-Presbyetrian Hospital
New York, New York, 10032, United States
Montefiore Medical Center
The Bronx, New York, 10467, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106, United States
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Cincinnati Children's Liberty Campus
Liberty Township, Ohio, 45044, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Oregon Health & Science University
Portland, Oregon, 97239, United States
Penn State Children's Hospital and Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
Buerger Center for Advanced Pediatric Care
Philadelphia, Pennsylvania, 19104, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Children's Blood and Cancer Center
Austin, Texas, 78723, United States
Dell Children's Medical Center
Austin, Texas, 78723, United States
Children's Medical Center Dallas
Dallas, Texas, 75235, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Cook Children's H/O Infusion Center
Grapevine, Texas, 76051, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Children's Medical Center Plano
Plano, Texas, 75024, United States
Intermountain - Primary Children's Hospital
Salt Lake City, Utah, 84113, United States
Primary Children's Hospital Outpatient Services
Salt Lake City, Utah, 84113, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
Children's Hospital of Richmond at VCU
Richmond, Virginia, 23219, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Wisconsin
Milwaukee, Wisconsin, 53226, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Hospital Pequeno Principe / A ssociacao Hospitalar de Protecao a Infancia
Curitiba, Paraná, 80250-060, Brazil
Hospital Pequeno Príncipe
Curitiba, Paraná, 80250-060, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90410000, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, São Paulo, 14784400, Brazil
Instituto Nacional de Câncer - INCA
Rio de Janeiro, 20230-130, Brazil
Hospital Santa Marcelina
São Paulo, 08270-070, Brazil
Alberta Children's Hospital
Calgary, Alberta, T3B 6A8, Canada
Stollery Children's Hospital
Edmonton, Alberta, T6G 2B7, Canada
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
CHU Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
Detska nemocnice FN Brno
Brno, Brno-město, 613 00, Czechia
Fakultni nemocnice v Motole
Prague, Praha 5, 150 06, Czechia
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux, Aquitaine, 33076, France
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69008, France
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, 69373 CEDEX 08, France
Gustave Roussy
Villejuif, Val-de-marne, 94800, France
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
Marseille, 13385, France
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, 45122, Germany
Artemis hospital
Gurugram, Haryana, 122001, India
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, 110029, India
Rajiv Gandhi Cancer Institute And Research Centre
New Delhi, National Capital Territory of Delhi, 110085, India
Instytut Matki i Dziecka
Warsaw, Masovian Voivodeship, 01-211, Poland
Detska fakultna nemocnica s poliklinikou Banska Bystrica
Banská Bystrica, 974 09, Slovakia
Narodny ustav detskych chorob
Bratislava, 83340, Slovakia
National Cancer Center
Goyang-si, Kyǒnggi-do, 10408, South Korea
Seoul National University Hospital
Seoul, Seoul-teukbyeolsi [seoul], 03080, South Korea
Asan Medical Center
Seoul, Seoul-teukbyeolsi [seoul], 05505, South Korea
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [seoul], 06351, South Korea
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], 08035, Spain
Hospital Infantil Universitario Niño Jesús
Madrid, Madrid, Comunidad de, 28009, Spain
Sahlgrenska Universitetssjukhuset Östra
Gothenburg, Västra Götalands LÄN [se-14], 416 50, Sweden
Ege Universitesi Hastanesi
Izmir, İ̇zmir, 35100, Turkey (Türkiye)
Hacettepe Universite Hastaneleri
Ankara, 06100, Turkey (Türkiye)
Royal Victoria Infirmary
Newcastle upon Tyne, England, NE1 4LP, United Kingdom
Royal Hospital for Children
Glasgow, Scotland, G51 4TF, United Kingdom
Leeds General Infirmary
Leeds, LS1 3EX, United Kingdom
University College London Hospital, NHS Foundation Trust
London, NW1 2PG, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
October 9, 2018
First Posted
October 17, 2018
Study Start
May 24, 2019
Primary Completion
August 26, 2024
Study Completion
October 18, 2025
Last Updated
January 14, 2025
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.