Carboxyamidotriazole in Treating Patients With Metastatic Kidney Cancer

Study Overview
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Brief Summary
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Randomized phase II trial to study the effectiveness of carboxyamidotriazole in treating patients who have metastatic kidney cancer. Carboxyamidotriazole may stop the growth of kidney cancer by stopping blood flow to the tumor

Detailed Description
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OBJECTIVES: I. Determine the toxicity and disease-stabilizing effect of carboxyamidotriazole in patients with metastatic renal cell carcinoma. II. Determine the objective response rate in patients treated with this drug. OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to time from diagnosis of metastatic disease to study entry (fewer than 24 months vs 24 months or more). Patients receive oral carboxyamidotriazole (CAI) daily for 4 weeks. Treatment repeats for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients experiencing complete or partial response continue treatment until disease progression or unacceptable toxicity. Patients with stable disease are randomized to one of two treatment arms. Arm I: Patients receive oral CAI as above. Arm II: Patients receive a placebo. Treatment repeats every 4 weeks for at least 4 courses in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression are unblinded and those on placebo begin oral CAI as above. Patients are followed every 6 months. PROJECTED ACCRUAL: A maximum of 335 patients will be accrued for this study within 15-25 months.

Official Title
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A Phase II Randomized Discontinuation Trial Of Carboxyaminoimidazole (CAI, NSC 609974) In Metastatic Renal Carcinoma

Conditions
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Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

Intervention / Treatment
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* Drug: carboxyamidotriazole
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed renal cell carcinoma Metastatic or unresectable disease Documented disease progression, even after nephrectomy At least 1 unidimensionally measurable lesion At least 20 mm by conventional techniques At least 10 mm by spiral CT scan The following lesions are not considered measurable: Bone lesions Leptomeningeal disease Ascites Pleural/pericardial effusion Abdominal masses not confirmed and followed by imaging Cystic lesions Performance status - CTC 0-2 WBC at least 2,000/mm^3 Platelet count at least 75,000/mm^3 Bilirubin no greater than upper limit of normal (ULN) AST no greater than 2.5 times ULN Creatinine no greater than 2.0 mg/dL Not pregnant or nursing Fertile patients must use effective contraception No baseline neuropathy or cerebellar dysfunction greater than grade 1 At least 4 weeks since prior immunotherapy No prior carboxyamidotriazole No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) Concurrent epoetin alfa allowed At least 4 weeks since prior chemotherapy No concurrent chemotherapy No concurrent hormonal therapy except steroids for adrenal failure or hormones for conditions not related to disease (e.g., insulin for diabetes) At least 4 weeks since prior radiotherapy No concurrent palliative radiotherapy See Disease Characteristics At least 4 weeks since prior surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (carboxyaminoimidazole)<br>Patients receive oral CAI daily for 4 weeks. Treatment repeats for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients experiencing complete or partial response continue treatment until disease progression or unacceptable toxicity. Patients receive oral CAI as above. | Drug: carboxyamidotriazole<br>* Given orally<br>* Other names: carboxyaminoimidazole;|
| Experimental: Arm II (carboxyamidotriazole, placebo)<br>Patients receive oral CAI daily for 4 weeks. Treatment repeats for 4 courses in the absence of disease progression or unacceptable toxicity. After 4 courses, patients experiencing complete or partial response continue treatment until disease progression or unacceptable toxicity. Patients receive a placebo. | Drug: carboxyamidotriazole<br>* Given orally<br>* Other names: carboxyaminoimidazole;Other: placebo<br>* Given orally<br>* Other names: PLCB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients progressing on placebo to the proportion progressing on CAI |  | Up to 16 weeks | 
| Proportions of patients with stable disease |  | Up to 16 weeks | 
| Objective response |  | Up to 16 weeks |