Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers

February 6, 2013 updated by: National Cancer Institute (NCI)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Cancer Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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: chemotherapy
Drug: ketoconazole
Drug: carboxyamidotriazole

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 1998

Primary Completion (Actual)

December 1, 2001

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

June 2, 2004

First Posted (Estimate)

June 3, 2004

Study Record Updates

Last Update Posted (Estimate)

February 7, 2013

Last Update Submitted That Met QC Criteria

February 6, 2013

Last Verified

February 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02265
  • UCCRC-9019
  • NCI-T97-0086
  • CDR0000066129 (Registry Identifier: PDQ (Physician Data Query))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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