Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
NCT ID: NCT03709680
Last Updated: 2025-01-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
128 participants
INTERVENTIONAL
2019-05-24
2025-10-18
Brief Summary
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
The palbociclib plus topotecan and cyclophosphamide will comprise of a dose determination cohort(following a modified rolling 6 design), a dose expansion cohort, and Neuroblastoma tumor -specific cohort.
Phase 2 open-label, randomized portion of the study will randomize patients in a 2:1 ratio to receive either palbociclib in combination with irinotecan and temozolomide (Arm A) or irinotecan and temozolomide chemotherapy alone (Arm B). Randomization will be stratified using block randomization by type and time of current disease recurrence (primary refractory or 1st recurrence \< 2 years versus 1st recurrence ≥ 2 years or 2nd or greater recurrence).
TREATMENT
NONE
Study Groups
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Phase 2 Arm A
Palbociclib in combination with irinotecan and temozolomide.
Palbociclib
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
Temozolomide
Phase 1 and Phase 2: Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
Irinotecan
Phase 1 and Phase 2: Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Phase 1
Palbociclib in combination with temozolomide and irinotecan and/or with topotecan and cyclophosphamide.
Palbociclib
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
Temozolomide
Phase 1 and Phase 2: Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
Irinotecan
Phase 1 and Phase 2: Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Topotecan
Phase 1 only : Administered at 0.75 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Cyclophosphamide
Phase 1 only: Administered at 250 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Phase 2 Arm B
Irinotecan and temozolomide alone.
Temozolomide
Phase 1 and Phase 2: Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
Irinotecan
Phase 1 and Phase 2: Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Phase 1 Tumor specific cohort - Neuroblastoma
Palbociclib in combination with topotecan and cyclophosphamide.
Palbociclib
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
Topotecan
Phase 1 only : Administered at 0.75 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Cyclophosphamide
Phase 1 only: Administered at 250 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Interventions
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Palbociclib
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
Temozolomide
Phase 1 and Phase 2: Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
Irinotecan
Phase 1 and Phase 2: Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Topotecan
Phase 1 only : Administered at 0.75 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Cyclophosphamide
Phase 1 only: Administered at 250 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
2. Age ≥2 and \<21 years at the time of study entry.
3. 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.
4. 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).
5. Adequate renal function: Serum creatinine level based on age/gender must within protocol specified limits.
6. 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).
7. Patients enrolled to Phase 1 portion of the study and tumor specific cohorts must have measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or at least evaluable disease by INRC for neuroblastoma.
The eligible patients with neuroblastoma must have at least one of the following at the time of study entry:
* Measurable tumor by CT or MRI that is avid on MIBG scan or demonstrates increased FDG uptake on PET scan;
* Avid lesion on MIBG scan with positive uptake at a minimum of one site;
* For disease that is not avid by MIBG-scan, at least one lesion that demonstrates increased FDG uptake on PET scan AND viable neuroblastoma confirmed by current or prior biopsy;
* bone marrow involvement with more than 5% neuroblastoma cells in at least one sample from bilateral bone marrow biopsies;
* In non MIBG-avid refractory soft tissue disease that does not demonstrate increased FDG uptake; lesion biopsy is required to document the presence of viable neuroblastoma, unless patient has a new soft tissue lesion (radiographic evidence of disease progression).
Patients with EWS enrolled to Phase 2 portion of the study are eligible with evaluable disease (eg, bone only disease with no soft tissue component).
8. Recovered to CTCAE Grade ≤1, or to baseline, from any non-hematological acute toxicities of prior surgery, chemotherapy, immunotherapy, radiotherapy, differentiation therapy or biologic therapy, with the exception of alopecia.
9. Serum/urine pregnancy test (for all girls ≥8 years of age) negative at screening and at the baseline visit.
Exclusion:
1. 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.
2. 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.
3. 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.)
4. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
5. Prior irradiation to \>50% of the bone marrow (see Appendix 9).
6. Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
7. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
8. 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.
9. 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.
10. 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.
11. Hereditary bone marrow failure disorder.
12. QTc \>470 msec.
13. 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);
* Diagnosed or suspected congenital or acquired prolonged QT syndrome;
* Need for medications known to prolong the QT interval;
* Uncorrected hypomagnesemia or hypokalemia because of potential effects on the QT interval;
* Left ventricular ejection fraction \<50% or shortening fraction \<28%.
14. Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
15. Evidence of serious active or uncontrolled bacterial, fungal or viral infection or known history of hepatitis B virus, hepatitis C virus, or human immunodeficiency virus infection or acquired immunodeficiency syndrome-related illness. Screening for viral hepatitis and HIV is under discretion of investigator unless required by local regulation.
16. Severe acute or chronic medical or laboratory test abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results, and in the judgment of the Investigator, would make the patient inappropriate for entry into this study.
17. Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or patients who are Pfizer employees, including their family members, directly involved in the conduct of the study.
18. Fertile male patients or female patients of childbearing potential who are unwilling or unable to follow contraceptive requirements.
19. Pregnant or breastfeeding women.
2 Years
20 Years
ALL
No
Sponsors
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Children's Oncology Group
NETWORK
Pfizer
INDUSTRY
Responsible Party
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Principal Investigators
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Pfizer CT.gov Call Center
Role: STUDY_DIRECTOR
Pfizer
Locations
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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
Children's Hospital Colorado
Aurora, Colorado, United States
Children's National Hospital
Washington D.C., District of Columbia, United States
UF Health Shands Hospital
Gainesville, Florida, United States
University of Florida College of Medicine
Gainesville, Florida, United States
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Johns Hopkins All Children's Outpatient Care Center
St. Petersburg, Florida, United States
Johns Hopkins All Children's Hospital
Tampa, Florida, United States
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, United States
Children's Healthcare of Atlanta at Scottish Rite
Atlanta, Georgia, United States
Children's Healthcare of Atlanta, Medical Office Building
Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States
Indiana University
Indianapolis, Indiana, United States
Norton Children's Hospital
Louisville, Kentucky, United States
Novak Center for Children's Health
Louisville, Kentucky, United States
Johns Hopkins University
Baltimore, Maryland, United States
University of Michigan Health System
Ann Arbor, Michigan, United States
University of Minnesota Masonic Children's Hospital
Minneapolis, Minnesota, United States
University of Minnesota Medical Center, Fairview
Minneapolis, Minnesota, United States
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, United States
University of Minnesota
Minneapolis, Minnesota, United States
University of Mississippi Medical Center
Jackson, Mississippi, United States
Children's Mercy Hospital
Kansas City, Missouri, United States
Washington University School of Medicine
St Louis, Missouri, United States
Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
John R. Oishei Childrens Hospital
Buffalo, New York, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Cohen Children's Medical Center
New Hyde Park, New York, United States
Morgan Stanley Children's Hospital of New York-Presbyetrian Hospital
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States
Nationwide Children's Hospital
Columbus, Ohio, United States
Cincinnati Children's Liberty Campus
Liberty Township, Ohio, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
Oregon Health & Science University
Portland, Oregon, United States
Penn State Children's Hospital and Penn State Health Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
Buerger Center for Advanced Pediatric Care
Philadelphia, Pennsylvania, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States
Children's Blood and Cancer Center
Austin, Texas, United States
Dell Children's Medical Center
Austin, Texas, United States
Children's Medical Center Dallas
Dallas, Texas, United States
Cook Children's Medical Center
Fort Worth, Texas, United States
Cook Children's H/O Infusion Center
Grapevine, Texas, United States
Texas Children's Hospital
Houston, Texas, United States
Children's Medical Center Plano
Plano, Texas, United States
Intermountain - Primary Children's Hospital
Salt Lake City, Utah, United States
Primary Children's Hospital Outpatient Services
Salt Lake City, Utah, United States
Children's Hospital of The King's Daughters
Norfolk, Virginia, United States
Children's Hospital of Richmond at VCU
Richmond, Virginia, United States
Seattle Children's Hospital
Seattle, Washington, United States
Children's Wisconsin
Milwaukee, Wisconsin, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Hospital Pequeno Principe / A ssociacao Hospitalar de Protecao a Infancia
Curitiba, Paraná, Brazil
Hospital Pequeno Príncipe
Curitiba, Paraná, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, Brazil
Fundação Pio XII - Hospital de Câncer de Barretos
Barretos, São Paulo, Brazil
Instituto Nacional de Câncer - INCA
Rio de Janeiro, , Brazil
Hospital Santa Marcelina
São Paulo, , Brazil
Alberta Children's Hospital
Calgary, Alberta, Canada
Stollery Children's Hospital
Edmonton, Alberta, Canada
The Hospital for Sick Children
Toronto, Ontario, Canada
CHU Sainte-Justine
Montreal, Quebec, Canada
Detska nemocnice FN Brno
Brno, Brno-město, Czechia
Fakultni nemocnice v Motole
Prague, Praha 5, Czechia
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
Bordeaux, Aquitaine, France
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, France
Centre Leon Berard
Lyon, Auvergne-Rhône-Alpes, France
Gustave Roussy
Villejuif, Val-de-marne, France
Assistance Publique Hôpitaux de Marseille - Hôpital de la Timone
Marseille, , France
Universitätsklinikum Essen
Essen, North Rhine-Westphalia, Germany
Artemis hospital
Gurugram, Haryana, India
All India Institute of Medical Sciences
New Delhi, National Capital Territory of Delhi, India
Rajiv Gandhi Cancer Institute And Research Centre
New Delhi, National Capital Territory of Delhi, India
Instytut Matki i Dziecka
Warsaw, Masovian Voivodeship, Poland
Detska fakultna nemocnica s poliklinikou Banska Bystrica
Banská Bystrica, , Slovakia
Narodny ustav detskych chorob
Bratislava, , Slovakia
National Cancer Center
Goyang-si, Kyǒnggi-do, South Korea
Seoul National University Hospital
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Asan Medical Center
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [seoul], South Korea
Hospital Universitari Vall d'Hebron
Barcelona, Barcelona [barcelona], Spain
Hospital Infantil Universitario Niño Jesús
Madrid, Madrid, Comunidad de, Spain
Sahlgrenska Universitetssjukhuset Östra
Gothenburg, Västra Götalands LÄN [se-14], Sweden
Ege Universitesi Hastanesi
Izmir, İ̇zmir, Turkey (Türkiye)
Hacettepe Universite Hastaneleri
Ankara, , Turkey (Türkiye)
Royal Victoria Infirmary
Newcastle upon Tyne, England, United Kingdom
Royal Hospital for Children
Glasgow, Scotland, United Kingdom
Leeds General Infirmary
Leeds, , United Kingdom
University College London Hospital, NHS Foundation Trust
London, , United Kingdom
Countries
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Related Links
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To obtain contact information for a study center near you, click here.
Other Identifiers
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A5481092
Identifier Type: -
Identifier Source: org_study_id
2024-511975-14-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
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