A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Investigation of Carboxyamido-triazole (CAI) Modulated by Ketoconozole In Patients With Advanced Malignancies
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Mark J. Ratain, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Chicago
Authority:
United States: Food and Drug Administration
Study ID:
NCI-2012-02265
NCT ID:
NCT00003249
Start Date:
May 1998
Completion Date:
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
Name | Location |
|---|---|
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
