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A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies


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

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.

Inclusion Criteria


- Histologically or cytologically proven refractory or recurrent nonhematologic

- Measurable or evaluable disease by radiographic or clinical examination


- 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


- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

Mark J. Ratain, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Chicago


United States: Food and Drug Administration

Study ID:




Start Date:

May 1998

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific



University of Chicago Cancer Research Center Chicago, Illinois  60637