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Phase I Study of Carboxyamidotriazole Modulated by Ketoconazole in Patients with Advanced Malignancies (Summary Last Modified 01/2001)

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs
Phase I Treatment Closed 18 and over NCI UCCRC-9019
NCI-T97-0086, NCT00003249, T97-0086

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.

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

Expected Enrollment

Up to 30 patients will be accrued for the study.

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.

Trial Contact Information

Trial Lead Organizations

University of Chicago Cancer Research Center

Mark Ratain, MD, Protocol chair
Ph: 773-702-4400; 888-824-0200

Registry Information

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

Trial Start Date		1998-05-21

Registered in ClinicalTrials.gov		NCT00003249

Date Submitted to PDQ		1998-03-05

Information Last Verified		2001-01-01

NCI Grant/Contract Number		U01-CA69852

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.