PBTC42: Palbociclib Isethionate in Treating Younger Patients With Recurrent, Progressive, or Refractory Central Nervous System Tumors

Phase I Study of CDK 4-6 Inhibitor PD-0332991 (palbociclib; IBRANCE) in Children with Recurrent, Progressive or Refractory Central Nervous System Tumors

Categories:

Brain Tumor

Phase I/II

Diseases Treated:

Retinoblastoma protein 1 (Rb1) positive recurrent, progressive, or refractory central nervous system tumors

Eligibility Overview:

  • Between 4 and 21 years old
  • Able to swallow capsules
  • Rb1-positive recurrent, progressive or refractory central nervous system (CNS) tumor or DIPG
  • Stable neurological deficit for at least 1 week prior to enrollment
  • Last dose of known myelosuppressive anticancer chemotherapy at least 3 weeks prior to enrollment
  • Last fraction of focal irradiation > 2 weeks prior to enrollment
  1. Brief Summary

    This Phase I clinical trial will study the side effects and best dose of palbociclib isethionate in treating younger patients with central nervous system tumors that have grown, come back or not responded to treatment. Palbociclib isethionate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

    Objectives

    • To find the highest dose of PD-0332991 that can be given safely without causing severe side effects
    • To learn what side effects may occur when PD-033291 is given
    • To learn how the body handles PD-0332991 by studying the levels of the drug in the blood

    Eligibility Criteria

    Screen inclusion criteria include:

    • Between 4 and 21 years old
    • Diagnosis of recurrent, refractory, or progressive central nervous system (CNS) tumor
    • Able to swallow capsules
    • Willing to provide pre-trial tumor material for Rb1 testing
    • Prior therapy:
      • Stratum I participants - Received 4 or more prior treatment regimens with either myelosuppressive chemotherapy or biologic agents and/or focal radiotherapy
      • Stratum II participants - Received more than 4 prior treatment regimens with either myelosuppressive chemotherapy or biologic agents and/or craniospinal irradiation and/or myeloablative chemotherapy with autologous stem cell rescue

    Screen exclusion criteria include:

    • Low grade glioma

    Treatment inclusion criteria include:

    • Between 4 and 21 years old at time of enrollment
    • Histologically confirmed Rb1 positive recurrent, progressive, or refractory CNS tumor or DIPG
    • Prior therapy:
      • Stratum I participants - Received 4 or more prior treatment regimens with either myelosuppressive chemotherapy or biologic agents and/or focal radiotherapy
      • Stratum II participants - Received more than 4 prior treatment regimens with either myelosuppressive chemotherapy or biologic agents and/or craniospinal irradiation and/or myeloablative chemotherapy with autologous stem cell rescue
    • Neurological deficit that is stable for at least 1 week prior to enrollment
    • Received last dose of known myelosuppressive anticancer chemotherapy at least 3 weeks prior to enrollment
    • Received last fraction of focal irradiation more than 2 weeks prior to enrollment
    • Received last fraction of craniospinal irradiation more than 3 months prior to enrollment (Stratum II only)

    Treatment exclusion criteria include:

    • Low grade glioma
    • Rb1 negative tumor
    • Requires enzyme inducing anti-convulsants to control seizures

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Other collaborating sites in the U.S.

  2. About this study

    This study will enroll patients who have a brain tumor that has grown (progressive), come back (recurrent), or has not responded to treatment (refractory). The study has two components: a screening phase and a treatment phase.

    Screening phase: The purpose of the screening phase is to perform a test on a sample of your tumor which was removed at a time of your previous surgery. The test will determine if the tumor has a specific protein called Rb1.

    Main treatment phase: The Rb1 protein stops malignant (cancer) tumor cells from growing and becoming cancer. Study participants will receive the experimental medicine called PD-0332991 (palbociclib; IBRANCE). This medicine has been previously tested in adults only. This study is the first time this drug is being given to children. The study doctor(s) will test different doses of the medicine to determine the highest dose that can be safely given to children with this type of tumor.

    Purpose of this clinical trial

    The main purpose of the study is to test the safety of PD-0332991 in children. Researchers also want to find out if PD-0332991 is a more effective treatment for many types of childhood brain tumors than current therapies.

  3. PBTC42 Quick View
    Sponsors St. Jude Children's Research Hospital
    ClinicalTrials.gov identifier NCT02255461
    Trial Start Date October 2014
    Estimated Enrollment 55
    Study Phase Phase I
    Conditions CNS tumors
    Ages 4 to 21 years old
    Principal investigator Zsila Sadighi, MD
    Study Sites St. Jude Children's Research Hospital and other collaborating sites in the U.S.
    For a consultation or to discuss PBTC42 St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Phone: 901-595-2544 or 901-595-4599
Fax: 901-595-6211

OR

Tabatha E. Doyle, RN
Coordinator, Brain Tumor Program
MS 260
262 Danny Thomas Place
Memphis, TN 38105
Phone: (901) 595-2544
FAX: (901) 595-6211

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.