PBTC-042 - Phase I Study of PD-0332991 in progressive CNS tumors

PBTC-042: Phase I Study of CDK 4-6 inhibitor PD-0332991 in children with recurrent, progressive or refractory central nervous system tumors

Diseases

Patients must have retinoblastoma protein (Rb1) positive recurrent, progressive or refractory central nervous system tumors.

Description

PD-0332991 is a highly-specific inhibitor of CDK4 and 6, which drive cell division. A screening test will be performed in patients for the presence of RB1, because this tumor suppressor protein is needed to control growth in these cells even if CDK4/6 are inhibited. PD-0332991 is taken orally once daily for 21 days followed by a week rest. Therapy may continue for up to two years in the absence of disease progression or unacceptable toxicity.

Eligibility Criteria

  • Patients must be between 4 and 21 years of age.
  • Patients must not have low grade gliomas or Rb1 negative tumors.
  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer chemotherapy and have the appropriate wash-out period from most recent cancer directed therapy.
  • Must have adequate organ function as evidenced by laboratory criteria and EKG.
  • Patients must be able to swallow capsules.
  • Patients must have received a maximum of than 2 prior chemotherapy regimens and/or focal radiotherapy.
  • Patients must not have received prior myeloablative chemotherapy with stem cell rescue, craniospinal irradiation, or treatment with a CDK inhibitor.
  • Patients must have available tumor tissue to assess Rb1 protein status, except for patients with diffuse intrinsic brain stem glioma.
  • Patients must have bi-dimensionally measurable disease.
  • Patients who are receiving corticosteroids must be on a stable or decreasing dose.
  • Patients must not be receiving any medications that are known to prolong QTc interval, strong inducers or inhibitors of CYP3A4, enzyme-inducing anticonvulsants, or other investigational agents.
  • Patients must not have cataracts on ophthalmologic examination.

Contact

For the current status and more detailed eligibility criteria of these clinical studies & protocols, referring physicians and families may call the Developmental Therapeutics Program directly at (832) 824-4266 at any time. Kate Mazur,RN, MSN, CPNP, a pediatric nurse practitioner for the Developmental Therapeutics Program, will answer any questions or concerns you may have. You may need to leave a voice mail, and she will return your call as soon as possible. She may also be reached by email at kamazur@txch.org.