Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors

NCT03709680

Last updated date
Study Location
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611-2991, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Solid Tumors, Ewing Sarcoma, Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Diffuse Intrinsic Pontine Glioma
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
2-21 years

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Solid Tumors, Ewing Sarcoma, Rhabdoid Tumor, Rhabdomyosarcoma, Neuroblastoma, Medulloblastoma, Diffuse Intrinsic Pontine GliomaStudy Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
NCT03709680
  1. Chicago, Illinois
  2. New York, New York
  3. Birmingham, Alabama
  4. Phoenix, Arizona
  5. Los Angeles, California
  6. Oakland, California
  7. Orange, California
  8. Palo Alto, California
  9. San Francisco, California
  10. San Francisco, California
  11. Aurora, Colorado
  12. Washington, District of Columbia
  13. Saint Petersburg, Florida
  14. Saint Petersburg, Florida
  15. Tampa, Florida
  16. Atlanta, Georgia
  17. Atlanta, Georgia
  18. Indianapolis, Indiana
  19. Louisville, Kentucky
  20. Louisville, Kentucky
  21. Baltimore, Maryland
  22. Boston, Massachusetts
  23. Ann Arbor, Michigan
  24. Ann Arbor, Michigan
  25. Minneapolis, Minnesota
  26. Minneapolis, Minnesota
  27. Minneapolis, Minnesota
  28. Minneapolis, Minnesota
  29. Jackson, Mississippi
  30. Kansas City, Missouri
  31. Omaha, Nebraska
  32. Hackensack, New Jersey
  33. New Brunswick, New Jersey
  34. New Brunswick, New Jersey
  35. New York, New York
  36. Winston-Salem, North Carolina
  37. Cincinnati, Ohio
  38. Cleveland, Ohio
  39. Cleveland, Ohio
  40. Columbus, Ohio
  41. Liberty Township, Ohio
  42. Oklahoma City, Oklahoma
  43. Portland, Oregon
  44. Hershey, Pennsylvania
  45. Hershey, Pennsylvania
  46. Philadelphia, Pennsylvania
  47. Philadelphia, Pennsylvania
  48. Philadelphia, Pennsylvania
  49. Pittsburgh, Pennsylvania
  50. Austin, Texas
  51. Austin, Texas
  52. Dallas, Texas
  53. Houston, Texas
  54. Plano, Texas
  55. Norfolk, Virginia
  56. Richmond, Virginia
  57. Seattle, Washington
ALL GENDERS
2 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Study Of Palbociclib Combined With Chemotherapy In Pediatric Patients With Recurrent/Refractory Solid Tumors
Official Title  ICMJE PHASE 1 STUDY TO EVALUATE THE SAFETY AND PHARMACOKINETICS OF PALBOCICLIB (IBRANCE(REGISTERED)) IN COMBINATION WITH IRINOTECAN AND TEMOZOLOMIDE AND IN COMBINATION WITH TOPOTECAN AND CYCLOPHOSPHAMIDE IN PEDIATRIC PATIENTS WITH RECURRENT OR REFRACTORY SOLID TUMORS
Brief Summary This study will evaluate palbociclib in combination with chemotherapy (temozolomide with irinotecan and topotecan with cyclophosphamide) in children, adolescents and young adults with recurrent or refractory solid tumors. The main purpose of this study is to evaluate the safety of palbociclib in combination with chemotherapy in order to estimate the maximum tolerated dose. Pharmacokinetics and efficacy of palbociclib in combination with chemotherapy will be evaluated.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

The palbociclib plus irinotecan and temozolomide combination part of the study will comprise of a dose escalation cohort (following a rolling 6 design), a dose expansion cohort, EWS tumor specific cohort and if applicable, other solid tumor-specific cohorts.

The palbociclib plus topotecan and cyclophosphamide will comprise of a dose determination cohort(following a modified rolling 6 design), a dose expansion cohort, and if applicable, other solid tumor-specific cohorts.

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumors
  • Ewing Sarcoma
  • Rhabdoid Tumor
  • Rhabdomyosarcoma
  • Neuroblastoma
  • Medulloblastoma
  • Diffuse Intrinsic Pontine Glioma
Intervention  ICMJE
  • Drug: Palbociclib
    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
    Other Name: Ibrance
  • Drug: Temozolomide
    Administered at 100 mg/m2 (oral or intravenous), on days 1-5 of a 21-day cycle
  • Drug: Irinotecan
    Administered at 50 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
  • Drug: Topotecan
    Administered at 0.75 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
  • Drug: Cyclophosphamide
    Administered at 250 mg/m2 (intravenous), on days 1-5 of a 21-day cycle
Study Arms  ICMJE Experimental: Single Arm
Palbociclib in combination with temozolomide and irinotecan Palbociclib in combination with topotecan and cyclophosphamide
Interventions:
  • Drug: Palbociclib
  • Drug: Temozolomide
  • Drug: Irinotecan
  • Drug: Topotecan
  • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 29, 2020)
133
Original Estimated Enrollment  ICMJE
 (submitted: October 15, 2018)
100
Estimated Study Completion Date  ICMJE January 21, 2025
Estimated Primary Completion Date December 3, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion:

  1. 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.
  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 ?100,000/mm3 (transfusion independent);
    • 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.
  7. Measurable disease as defined by RECIST version 1.1 or modified RANO criteria for CNS disease or INRC for neuroblastoma.
  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.
  10. Evidence of a personally signed and dated informed consent document indicating that the patient or a legally acceptable representative/parent(s)/legal guardian of minors, has been informed of all pertinent aspects of the study. Minor study patients also must provide age appropriate assent according to the local guidelines, where applicable.
  11. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other procedures.

Exclusion:

  1. 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.
  2. Prior intolerability to IRN and/or TMZ, for palbociclib with IRN and TMZ combination and prior intolerability to TOPO and/or CTX for palbociclib with TOPO and CTX combination.
  3. Use of strong cytochrome P450 (CYP) 3A inhibitors or inducers. 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. Prior growth factors (including filgrastim) within 7 days before study entry or PEG-filgrastim within 14 days before study entry.
  5. Radiation therapy within 14 days before study entry.
  6. Systemic anti cancer therapy within 2 weeks prior to study entry and 6 weeks for nitrosoureas.
  7. Previous high dose chemotherapy requiring stem cell rescue within 90 days or persistent AE >Grade 1.
  8. Prior irradiation to >50% of the bone marrow (see Appendix 9).
  9. Participation in other studies involving investigational drug(s) within 2 weeks or 5 half lives, whichever is longer, prior to study entry.
  10. Major surgery within 4 weeks prior to study entry. Surgical biopsies or central line placement are not considered major surgeries.
  11. Known or suspected hypersensitivity to palbociclib, IRN and/or TMZ.
  12. 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.
  13. 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.
  14. Hereditary bone marrow failure disorder.
  15. QTc >470 msec.
  16. 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%.
  17. Recent or ongoing clinically significant gastrointestinal disorder that may interfere with absorption of orally administered drugs (eg, gastrectomy).
  18. 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.
  19. Other 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.
  20. 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.
  21. Fertile male patients and female patients of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 90 after the last dose of investigational product.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 2 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03709680
Other Study ID Numbers  ICMJE A5481092
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Plan Description: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/d….
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP