Official Title: “A Phase I Investigation of Carboxyamido-Triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies”

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.

Study Type: Interventional

Study Design: Treatment

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.

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.

Intervention(s) in this Clinical Trial

• Drug: carboxyamidotriazole
• Drug: ketoconazole
• Procedure: chemotherapy

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Chicago

Overall Clinical Trial Officials and Contacts

Mark J. Ratain, MD Study Chair University of Chicago  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00003249

Study ID Number: CDR0000066129

ClinicalTrials.gov Identifier: NCT00003249

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database