Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

Inclusion Criteria

• •Histologically confirmed CNS malignancy at original diagnosis or relapse
• •* Histologic confirmation not required for patients with intrinsic brain stem tumors, optic pathway gliomas, or pineal tumors provided CSF or serum tumor markers, including alpha-fetoprotein orbeta-HCG, are elevated
• •* Recurrent or refractory spinal cord tumors allowed
• •Measurable or evaluable disease
• •No known curative therapy or therapy proven to prolong survival with an acceptable quality of life
• •Karnofsky performance status (PS) 50-100% (for patients \> 16 years of age) OR Lansky PS 50-100% (for patients ≤ 16 years of age)
• •* Neurological deficits must have been relatively stable for ≥ 1 week before study entry
• •* Patients unable to walk due to paralysis, but who are up in a wheelchair, are considered ambulatory for the purpose of assessing performance status
• •ANC ≥ 1,000/μL
• •Platelet count ≥ 100,000/μL (transfusion independent, defined as no platelet transfusion within the past 7 days)
• •Hemoglobin ≥ 8.0 g/dL (RBC transfusions allowed)
• •Creatinine clearance or radioisotope GFR ≥ 70mL/min OR maximum serum creatinine based on age and/or gender as follows:
• •* 0.6 mg/dL (1 year of age)
• •* 0.8 mg/dL (2 to 5 years of age)
• •* 1.0 mg/dL (6 to 9 years of age)
• •* 1.2 mg/dL (10 to 12 years of age)
• •* 1.5 mg/dL (males) or 1.4 mg/dL (females) (13 to 15 years of age)
• •* 1.7 mg/dL (males) or 1.4 mg/dL (females) (≥ 16 years of age)
• •Bilirubin ≤ 1.5 times upper limit of normal
• •ALT ≤ 110 U/L
• •Serum albumin ≥ 2 g/dL
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •Able to swallow capsules or liquid
• •Seizure disorder allowed provided it is well controlled with nonenzyme-inducing anticonvulsants
• •No pre-existing QTc ≥ 450 msec
• •No uncontrolled infection
• •No patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of study
• •Fully recovered from prior chemotherapy, immunotherapy, or radiotherapy
• •More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosourea)
• •At least 7 days since prior hematopoietic growth factors
• •At least 7 days since prior biologic agent (antineoplastic agent)
• •At least 7 days or 3 half-lives, whichever is longer, since prior monoclonal antibodies
• •More than 2 weeks since prior local palliative radiotherapy (small port)
• •At least 6 months since prior total-body radiotherapy (TBI), craniospinal radiotherapy, or radiotherapy to ≥ 50% of the pelvis
• •At least 6 weeks since other prior substantial bone marrow radiotherapy
• •At least 3 months since prior stem cell transplantation or rescue (without TBI)
• •* No evidence of active graft-vs-host disease
• •At least 2 weeks since prior valproic acid
• •No prior vorinostat
• •Prior temozolomide allowed provided there was no progressive disease during or within 1 month after completion of treatment
• •Concurrent corticosteroids allowed provided patient has been on a stable or decreasing dose for ≥ 7 days before study entry
• •No other concurrent investigational drugs
• •No other concurrent anticancer agents, including chemotherapy, radiotherapy, immunotherapy, or biologic therapy
• •No concurrent enzyme-inducing anticonvulsants