Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003249
First received: November 1, 1999
Last updated: February 6, 2013
Last verified: February 2013
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: carboxyamidotriazole
Drug: chemotherapy
Drug: ketoconazole
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Enrollment: 30
Study Start Date: May 1998
Primary Completion Date: December 2001 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003249

Locations
United States, Illinois
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
Investigators
Study Chair: Mark J. Ratain, MD University of Chicago
  More Information

Additional Information:
No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003249     History of Changes
Other Study ID Numbers: NCI-2012-02265, UCCRC-9019, NCI-T97-0086, CDR0000066129
Study First Received: November 1, 1999
Last Updated: February 6, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Carboxyamido-triazole
Ketoconazole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014