Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers

NCT ID: NCT00003249

Last Updated: 2013-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-05-31

Brief Summary

Phase I trial to study the effectiveness of carboxyamidotriazole and ketoconazole in treating patients with advanced cancers. 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.

Detailed Description

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.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm I

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.

Group Type: EXPERIMENTAL

carboxyamidotriazole

Intervention Type: DRUG

chemotherapy

Intervention Type: DRUG

ketoconazole

Intervention Type: DRUG

Interventions

carboxyamidotriazole

Intervention Type: DRUG

chemotherapy

Intervention Type: DRUG

ketoconazole

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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%
• Absolute neutrophil count at least 2,000/mm3
• Platelet count at least 100,000/mm3
• 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
• Creatinine no greater than 1.5 mg/dL OR creatinine clearance greater than 60 mL/min
• No concurrent neurotoxicities greater than grade 1 from previous chemotherapy
• No concurrent neuropathy greater than grade 1
• 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:

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark J. Ratain, MD

Role: STUDY_CHAIR

University of Chicago

Locations

University of Chicago Cancer Research Center

Chicago, Illinois, United States

Countries

United States

Other Identifiers

UCCRC-9019

Identifier Type: -

Identifier Source: secondary_id

NCI-T97-0086

Identifier Type: -

Identifier Source: secondary_id

CDR0000066129

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02265

Identifier Type: -

Identifier Source: org_study_id