Carboxyamidotriazole in Treating Patients With Metastatic Kidney Cancer

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

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

Study Overview

• Status: Completed
• Conditions: Stage IV Renal Cell Cancer; Recurrent Renal Cell Cancer
• Intervention / Treatment: Other: placebo; Drug: carboxyamidotriazole

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 335
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60606
      • Cancer and Leukemia Group B

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (carboxyaminoimidazole); 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; Given orally; Other Names: CAI; carboxyamido-triazole; carboxyaminoimidazole
Experimental: Arm II (carboxyamidotriazole, placebo); 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.	Other: placebo; Given orally; Other Names: PLCB; Drug: carboxyamidotriazole; Given orally; Other Names: CAI; carboxyamido-triazole; carboxyaminoimidazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Walter Stadler, Cancer and Leukemia Group B

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): October 1, 2005

Study Registration Dates

• First Submitted: November 6, 2000
• First Submitted That Met QC Criteria: July 25, 2003
• First Posted (Estimate): July 28, 2003

Study Record Updates

• Last Update Posted (Estimate): January 16, 2013
• Last Update Submitted That Met QC Criteria: January 15, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Carboxyamido-triazole
• Other Study ID Numbers: NCI-2012-02364; U10CA031946 (U.S. NIH Grant/Contract); CLB-69901; CDR0000068317 (Registry Identifier: PDQ (Physician Data Query))