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

November 1, 1999
February 6, 2013
May 1998
December 2001   (final data collection date for primary outcome measure)
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Not Provided
Complete list of historical versions of study NCT00003249 on ClinicalTrials.gov Archive Site
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Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers
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.

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.

Interventional
Phase 1
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Unspecified Adult Solid Tumor, Protocol Specific
  • Drug: carboxyamidotriazole
  • Drug: chemotherapy
  • Drug: ketoconazole
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.
Interventions:
  • Drug: carboxyamidotriazole
  • Drug: chemotherapy
  • Drug: ketoconazole
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
Not Provided
December 2001   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00003249
NCI-2012-02265, UCCRC-9019, NCI-T97-0086, CDR0000066129
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Study Chair: Mark J. Ratain, MD University of Chicago
National Cancer Institute (NCI)
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP