Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003249

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: carboxyamidotriazole Drug: chemotherapy Drug: ketoconazole	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of carboxyamidotriazole (CAI) in combination with ketoconazole in patients with advanced malignancies.
Evaluate the toxic effects, safety, and efficacy of CAI in combination with ketoconazole.
Determine the modulatory effects of ketoconazole on the pharmacokinetic profile of CAI.
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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 1998

Actual Primary Completion Date :

Dec 1, 2001

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: carboxyamidotriazole Drug: chemotherapy Drug: ketoconazole

Arm

Intervention/Treatment

Experimental: Arm I

Drug: carboxyamidotriazole

Drug: chemotherapy

Drug: ketoconazole

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair: Mark J. Ratain, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

National Cancer Institute (NCI)

ClinicalTrials.gov Identifier:

NCT00003249

Other Study ID Numbers:

NCI-2012-02265
UCCRC-9019
NCI-T97-0086
CDR0000066129

First Posted:

Jun 3, 2004

Last Update Posted:

Feb 7, 2013

Last Verified:

Feb 1, 2013

Keywords provided by National Cancer Institute (NCI)

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Ketoconazole

Carboxyamido-triazole

Study Results

No Results Posted as of Feb 7, 2013