Carboxyamidotriazole and Ketoconazole in Treating Patients With Advanced Cancers
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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 |
| 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 |
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 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:
|
Ketoconazole Carboxyamido-triazole 14-alpha Demethylase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antifungal Agents |
Anti-Infective Agents Therapeutic Uses Antineoplastic Agents Calcium Channel Blockers Membrane Transport Modulators Cardiovascular Agents |
ClinicalTrials.gov processed this record on May 16, 2013