RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of carboxyamidotriazole and ketoconazole in treating patients with advanced cancers.

Condition	Treatment or Intervention	Phase
unspecified adult solid tumor, protocol specific	Drug: carboxyamidotriazole  Drug: ketoconazole	Phase I

Further Study Details: 

OBJECTIVES: I. Determine the maximum tolerated dose of carboxyamidotriazole (CAI) in combination with ketoconazole in patients with advanced malignancies. II. Evaluate the toxic effects, safety, and efficacy of CAI in combination with ketoconazole. III. Determine the modulatory effects of ketoconazole on the pharmacokinetic profile of CAI. IV. Determine a pharmacodynamic model for CAI and ketoconazole with respect to potential gastrointestinal, hematologic, and neurotoxicities.

PROTOCOL OUTLINE: This is a dose escalation study. Patients receive oral carboxyamidotriazole (CAI) as a test dose on day 1. Patients receive oral ketoconazole on day 7, followed by CAI plus ketoconazole on day 8. CAI and ketoconazole are administered in combination on day 1 and days 3-28 of the first course. Ketoconazole is administered alone on day 2 of the first course. Subsequent courses begin at 28 day intervals in the absence of disease progression or unacceptable toxic effects. Cohorts of 3 patients are evaluated at each dose level prior to dose escalation. If one of three patients within a cohort experiences dose limiting toxicity (DLT), that dose level is expanded to incorporate six patients. If two or more patients experience DLT, the next lower dose is declared to be the maximum tolerated dose.

PROJECTED ACCRUAL: Up to 30 patients will be accrued for the study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically proven refractory or recurrent nonhematologic malignancies
• Measurable or evaluable disease by radiographic or clinical examination

--Prior/Concurrent Therapy--

• Biologic therapy: No concurrent isoniazid; No concurrent rifampin
• Chemotherapy: At least 4 weeks since chemotherapy; At least 6 weeks since nitrosoureas therapy; At least 3 months since suramin therapy; No prior carboxyamidotriazole
• Endocrine therapy: No concurrent steroids (except dose required for adrenal insufficiency); No concurrent tamoxifen
• Radiotherapy: No prior radiotherapy within 4 weeks of study
• Surgery: No prior total gastrectomy or total ileocolectomy
• Other: No concurrent therapy with H2 antagonists, barbiturates, calcium channel blockers, terfenadine, astemizole, cisapride, digitoxin, quinidine, amiodarone, carbamazepine, imipramine, or antacids; No concurrent erythromycin

--Patient Characteristics--

• Age: 18 and over
• Performance Status: Karnofsky 70-100%
• Life Expectancy: Not specified
• Hematopoietic: Absolute neutrophil count at least 2,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin no greater than 1.5 mg/dL; SGOT and SGPT no greater than 2.5 times upper limit of normal; Albumin at least 3 g/dL
• Renal: Creatinine no greater than 1.5 mg/dL OR Creatinine clearance greater than 60 mL/min
• Neurologic: No concurrent neurotoxicities greater than grade 1 from previous chemotherapy; No concurrent neuropathy greater than grade 1
• Other: Not pregnant; Effective contraceptive method must be used by fertile patients during and up to 2 months after study; No serious uncontrolled medical illness; No history of active inflammatory bowel disease, ileus, or other chronic malabsorption syndromes

Illinois
      University of Chicago Cancer Research Center, Chicago,  Illinois,  60637,  United States

Study chairs or principal investigators

Mark J. Ratain,  Study Chair,  University of Chicago Cancer Research Center   

Study ID Numbers:  CDR0000066129; UCCRC-9019; NCI-T97-0086
Record last reviewed:  June 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003249
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08