Patient case: 65-year-old female with melanoma; genetic feature: KIT (L576P)

Clinical trial: Carboxyamidotriazole and Paclitaxel in Treating Patients With Advanced Solid Tumors or Refractory Lymphomas

Summary: RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.
  PURPOSE: This phase I trial is studying the side effects and best dose of carboxyamidotriazole and paclitaxel in treating patients with advanced solid tumors or refractory lymphomas.

Detailed description: OBJECTIVES:
  -  Determine the maximum tolerated dose of paclitaxel when combined with carboxyamidotriazole in patients with advanced solid tumors or refractory lymphomas.
  -  Determine the pharmacokinetics and toxicities of this regimen in these patients.
  -  Identify diseases for which this combination appears active.
  OUTLINE: This is a dose escalation study.
  Patients receive oral carboxyamidotriazole (CAI) daily with paclitaxel IV over 3 hours on day 8 and every 3 weeks thereafter. Course 1 is 28 days and all other subsequent courses are 21 days. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients who achieve complete response receive 2 additional courses of treatment.
  Sequential dose escalation of CAI is followed by sequential dose escalation of paclitaxel. Dose escalation in cohorts of 3 to 6 patients each continues until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicity.
  PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Eligibility: DISEASE CHARACTERISTICS:
  -  Histologically diagnosed solid tumor (i.e., breast and ovarian epithelial carcinomas) or lymphoma
  -  Slides reviewed at the NCI Laboratory of Pathology
  -  Failure on therapy of proven efficacy for the disease
  -  Prior therapy not required for the following metastatic diseases:
  -  Melanoma
  -  Non-small cell lung cancer
  -  Renal cell carcinoma
  -  No brain metastases
  -  Primary brain tumors (such as glioblastoma multiforme) with stable neurologic deficits allowed
  -  Measurable or evaluable disease required
  -  Demonstrated by physical exam or on radiograph within 2 weeks prior to initiation of treatment OR
  -  Elevated PSA associated with prostate cancer
  -  Other marker-only disease ineligible
  PATIENT CHARACTERISTICS:
  Age:
  -  Over 18
  Performance status:
  -  ECOG 0-2
  Life expectancy:
  -  At least 3 months
  Hematopoietic:
  -  WBC at least 3,000/mm^3
  -  Platelet count at least 100,000/mm^3
  -  Hematocrit at least 27%
  Hepatic:
  -  Liver function tests no greater than 2 times upper limit of normal
  -  Bilirubin normal
  -  PT or PTT no greater than 1.25 times upper limit of normal
  -  Clotting parameters normal
  -  No concurrent anticoagulants other than 1 mg of warfarin per day for prophylaxis
  Renal:
  -  Creatinine no greater than 1.5 mg/dL OR
  -  Creatinine clearance at least 45 mL/min
  -  No kidney obstruction
  Cardiovascular:
  -  No cardiac conduction defect requiring antiarrhythmics
  -  No evidence of myocardial infarction or other myocardial damage within past 6 months
  Other:
  -  HIV negative
  -  No concurrent infection
  -  No guaiac-positive stool test
  -  No neuropathy greater than grade I (unless associated with fixed-deficit primary brain tumors)
  -  Not pregnant or nursing
  -  Fertile patients must use effective contraception during and for 2 months after study
  PRIOR CONCURRENT THERAPY:
  -  Recovery from prior therapy required
  Biologic therapy:
  -  At least 4 weeks since prior biologic therapy
  Chemotherapy:
  -  At least 4 weeks since prior chemotherapy (6 weeks since mitomycin, nitrosoureas, or carboplatin)
  -  No progression on carboxyamidotriazole or paclitaxel
  -  At least 6 months between treatment and relapse
  Endocrine therapy:
  -  At least 4 weeks since prior hormonal therapy
  -  No concurrent corticosteroids except as physiologic replacement
  Radiotherapy:
  -  At least 4 weeks since prior radiotherapy
  Surgery:
  -  Not specified
  Other:
  -  At least 1 week since prior therapeutic antibiotics
  -  Concurrent prophylactic antibiotics allowed except imidazole antifungals (e.g., ketoconazole, fluconazole)
  -  No concurrent calcium channel blockers

Relevance to patient case: not relevant