Patient case: 64-year-old male with Cholangiocarcinoma. Genetic variant: IDH1 (R132H). Other conditions: Neuropathy.

Clinical trial: CC-8490 in Treating Patients With Recurrent or Refractory High-Grade Gliomas

Summary: RATIONALE: Drugs used in chemotherapy, such as CC-8490, work in different ways to stop tumor cells from dividing so they stop growing or die.
  PURPOSE: Phase I trial to study the effectiveness of CC-8490 in treating patients who have recurrent or refractory high-grade gliomas.

Detailed description: OBJECTIVES:
  Primary
  -  Determine the maximum tolerated dose of CC-8490 in patients with recurrent or refractory high-grade gliomas.
  -  Determine, preliminarily, the toxic effects of this drug in these patients.
  -  Determine the pharmacokinetics of this drug in these patients.
  Secondary
  -  Determine, preliminarily, the potential anti-glioma activity of this drug in these patients.
  OUTLINE: This is a dose-escalation study.
  Patients receive oral CC-8490 once daily on days 1 and 3-28 (course 1 only). Beginning with course 2 and for all subsequent courses, patients receive oral CC-8490 once daily on days 1-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
  Cohorts of 3-6 patients receive escalating doses of CC-8490 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, a total of 10 patients are treated at that dose.
  Patients are followed within 2 weeks.
  PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically confirmed supratentorial malignant glioma, including any of the following:
  -  Glioblastoma multiforme
  -  Gliosarcoma
  -  Anaplastic astrocytoma
  -  Anaplastic oligodendroglioma
  -  Anaplastic mixed oligoastrocytoma
  -  Malignant glioma/astrocytoma not otherwise specified OR
  -  Clinical and radiographic diagnosis of progressive low-grade glioma
  -  Radiographically diagnosed infiltrating brain stem gliomas not amenable to biopsy allowed
  -  Recurrent or progressive disease as determined by 1 of the following:
  -  CT scan or MRI within the past 21 days
  -  Biopsy within the past 12 weeks
  -  Failed prior radiotherapy
  PATIENT CHARACTERISTICS:
  Age
  -  18 and over
  Performance status
  -  Karnofsky 60-100%
  Life expectancy
  -  More than 8 weeks
  Hematopoietic
  -  Granulocyte count at least 1,500/mm^3
  -  Platelet count at least 100,000/mm^3 (transfusion independent)
  -  Hemoglobin at least 8 g/dL (transfusion allowed)
  Hepatic
  -  Bilirubin no greater than 1.5 mg/dL
  -  AST and ALT no greater than 2 times upper limit of normal
  -  No significant active hepatic disease that would preclude study participation
  Renal
  -  Creatinine no greater than 1.5 mg/dL OR
  -  Creatinine clearance at least 60 mL/min
  -  No significant active renal disease that would preclude study participation
  Cardiovascular
  -  No significant active cardiac disease that would preclude study participation
  Other
  -  Not pregnant or nursing
  -  Negative pregnancy test
  -  Fertile patients must use effective contraception during and for 2 months after study participation
  -  No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
  -  No significant active psychiatric disease that would preclude study participation
  -  No other condition or laboratory abnormality that would preclude study participation
  -  Able to swallow capsules whole
  PRIOR CONCURRENT THERAPY:
  Biologic therapy
  -  At least 2 weeks since prior interferon
  -  No concurrent immunotherapy
  Chemotherapy
  -  At least 2 weeks since prior vincristine
  -  At least 3 weeks since prior procarbazine
  -  At least 4 weeks since prior temozolomide or carboplatin
  -  At least 6 weeks since prior nitrosoureas
  -  No other concurrent anticancer chemotherapy
  Endocrine therapy
  -  At least 2 weeks since prior tamoxifen
  -  Concurrent steroids allowed provided dose has been stable for at least 5 days prior to study enrollment
  Radiotherapy
  -  See Disease Characteristics
  -  At least 2 weeks since prior radiotherapy
  -  No concurrent radiotherapy
  Surgery
  -  At least 2 weeks since prior resection of a recurrent or progressive tumor
  Other
  -  At least 2 weeks since other prior non-cytotoxic therapy
  -  At least 4 weeks since other prior cytotoxic therapies
  -  More than 28 days since prior experimental study drugs
  -  No other concurrent investigational agents

Relevance to patient case: not relevant