Carboxyamidotriazole in Treating Patients With Stage III or Stage IV Non-small Cell Lung Cancer

Phase III Randomized, Double-Blind Study of CAI and Placebo in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Randomized phase III trial to determine the effectiveness of carboxyamidotriazole in treating patients who have stage III or stage IV non-small cell lung cancer. Chemotherapeutic agents are modestly effective for the treatment of advanced lung cancer, with rapid tumor relapse and growth even after initial response to therapy. It is not yet known whether carboxyamidotriazole is more effective than no further treatment after standard chemotherapy for non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IV Non-small Cell Lung Cancer
• Intervention / Treatment: Other: laboratory biomarker analysis; Procedure: quality-of-life assessment; Other: placebo; Drug: carboxyamidotriazole

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether oral administration of the carboxyaminoimidazole (CAI) is more effective than placebo in prolonging the overall survival in patients with non-small cell lung cancer stage III or stage IV non-small cell lung cancer who have been stable or had tumor regression following chemotherapy.

SECONDARY OBJECTIVES:

I. To evaluate the safety and tolerability of oral CAI following chemotherapy. II. To determine whether CAI prolongs time-to-disease progression relative to a placebo.

III. To evaluate whether a substantive effect in quality of life (QOL) can be detected between the CAI and placebo groups using the FACT-L and the UNISCALE.

IV. To document the response rate to CAI in patients with measurable or evaluable disease.

TERTIARY OBJECTIVES:

I. To evaluate genotypes at GSH-related loci as predictors of overall survival.

OUTLINE: This is a randomized, double-blind, multicenter study. Patients are stratified according to timing of first-line therapy (prior to registration vs after registration), disease stage (IIIA vs IIIB vs IV), therapy components (chemotherapy and thoracic radiotherapy vs chemotherapy only), ECOG performance status (0 vs 1 vs 2) and participating center. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive oral carboxyamidotriazole daily.

ARM II: Patients receive oral placebo daily.

Treatment continues in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then monthly during study.

Patients are followed every 3 months for 5 years.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • North Central Cancer Treatment Group

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:

• TRACK I: Histologically or cytologically confirmed NSCLC stage III or IV; disease must be stable or responding after standard chemotherapy (with or without TRT) for a minimum of 3 or a maximum of 6 months
• TRACK I: Not required to have measurable or evaluable disease at study entry
• TRACK I: Must have had one and only one prior chemotherapy regimen for NSCLC (radiosensitizers are allowed)
• TRACK I: =< 6 weeks from last dose of chemotherapy or TRT
• TRACK I: ECOG PS 0, 1, or 2
• TRACK I: ANC >= 1500/mm^3
• TRACK I: PLT >= 100,000/mm^3
• TRACK I: HgB >= 10.0 g/dL
• TRACK I: Total bilirubin =< 1.5 x UNL
• TRACK I: Alkaline phosphatase =< 3 x UNL
• TRACK I: AST =< 3 x UNL
• TRACK I: Creatinine =< 1.5 x UNL
• TRACK I: Expected survival of at least three months
• TRACK II AT REGISTRATION: Histologically or cytologically confirmed NSCLC stage III or IV
• TRACK II AT REGISTRATION: No prior chemotherapy for NSCLC
• TRACK II AT REGISTRATION: Expected survival of at least six months
• TRACK II AT REGISTRATION: Willingness to provide blood sample
• TRACK II AT RANDOMIZATION: STAB, PR, CR, REGR following 3-6 months of chemotherapy with or without radiation therapy
• TRACK II AT RANDOMIZATION: Must have had one and only one prior chemotherapy regimen for NSCLC (radiosensitizers are allowed)
• TRACK II AT RANDOMIZATION: =< 6 weeks from last dose of chemotherapy or TRT
• TRACK II AT RANDOMIZATION: ECOG PS 0, 1, or 2
• TRACK II AT RANDOMIZATION: ANC >= 1500/mm^3
• TRACK II AT RANDOMIZATION: PLT >= 100,000/mm^3
• TRACK II AT RANDOMIZATION: HgB >= 10.0 g/dL
• TRACK II AT RANDOMIZATION: Total bilirubin =< 1.5 x UNL
• TRACK II AT RANDOMIZATION: Alkaline phosphatase =< 3 x UNL
• TRACK II AT RANDOMIZATION: AST =< 3 x UNL
• TRACK II AT RANDOMIZATION: Creatinine =< 1.5 x UNL
• TRACK II AT RANDOMIZATION: Expected survival of at least three months

Exclusion Criteria:

• TRACK I: Pregnant, nursing women, females or sexual partners of childbearing potential not using adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) while on study treatment and for two months after discontinuing study treatment as this regimen may be harmful to a developing fetus or nursing child
• TRACK I: Untreated brain metastases
• TRACK I: Concomitant participation in a phase III lung cancer treatment trial
• TRACK I: Planned concurrent chemotherapy, immunotherapy or radiotherapy
• TRACK II AT RANDOMIZATION: Pregnant, nursing women, females or sexual partners of childbearing potential not using adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.) while on study treatment and for two months after discontinuing study treatment as this regimen may be harmful to a developing fetus or nursing child
• TRACK II AT RANDOMIZATION: Untreated brain metastases
• TRACK II AT RANDOMIZATION: Planned concurrent chemotherapy, immunotherapy, or radiotherapy

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 (CAI); Patients receive oral carboxyamidotriazole daily.	Other: laboratory biomarker analysis; Correlative studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Drug: carboxyamidotriazole; Given PO; Other Names: CAI; carboxyamido-triazole; carboxyaminoimidazole
Placebo Comparator: Arm II (placebo); Patients receive oral placebo daily	Other: laboratory biomarker analysis; Correlative studies; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Other: placebo; Given PO; Other Names: PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS was defined as the time from randomization to death of any cause. Participants who did not die or were lost to follow-up were censored at the time of last evaluation/follow-up date. Patients were followed for a maximum of 5 years from randomization. The median OS with 95%CI was estimated using the Kaplan Meier method.	up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Severe Non-hematologic Adverse Events	Severe non-hematologic adverse events were defined as adverse events grade 3 or higher, regardless of attribution to study drug. Adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC version 2.0)	every cycle during treatment
Time to Disease Progression (TTP)	TTP is defined as the time from randomization to first documented disease progression(PD). Patients who were lost to follow-up were censored at the time of last evaluation. For patients who died without clear documentation, PD was assumed at the midpoint of the time interval between last evaluation and death. Median TTP was estimated using the Kaplan Meier method. Measurable PD: ≥25% increase in the sum of the products of two greatest perpendicular diameters of all indicator lesions or appearance of new lesion(s). Evaluable PD: definite increase in tumor size or appearance of new lesion(s)	up to 5 years
Clinically Significant (10-point) Decrease in UNISCALE Quality of Life (QOL)Assessment From Baseline to Week 8	The UNISCALE was used to assess QOL. UNISCALE is a single item global measure of QOL. Participant were to complete the questionnaire at baseline and every 8 weeks, prior to assessment by the treating physician. A high score indicates a higher quality of life while a low score represents a lower quality of life. A 10 point or greater decline (from baseline to week 8) in UNISCALE QOL score was considered clinically significant.	Baseline to week 8
Clinically Significant (10-point) Decrease in Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L) Quality of Life (QOL)Assessment From Baseline to Week 8	The FACT-L is a 36-item Likert instrument that combines frequency of symptomatic/QOL problems with perceived relative importance of each issue. It includes 4 constructs of well being: physical, social/family, emotional and functional, and a fifth construct, additional concerns, dealing solely with tumor related symptoms. Questionnaires were completed at baseline and 8 weeks. Questions within each construct were summated to obtain a construct score. A higher score relates to higher quality of life. A 10 point or greater decline (from baseline to week 8) was considered clinically significant.	Baseline to week 8
Number of Patients With a Confirmed Tumor Responses Treated With CAI.	Confirmed response was defined as a complete response (CR) or partial response (PR) for patients with measurable disease or as a CR or regression (REGR) for patients with evaluable disease noted on 2 consecutive evaluations at least 4 weeks apart.; CR: total disappearance of all tumor;; PR: >=50% reduction of the sum of the products of the two greatest perpendicular diameters of all indicator lesions;; REGR: Definite decrease in tumor size and no new lesion(s).	During Treatment (up to 5 years)

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Edith Perez, North Central Cancer Treatment Group

Study record dates

Study Major Dates

• Study Start: April 1, 1999
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 20, 2014
• Last Update Submitted That Met QC Criteria: May 2, 2014
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; 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-2012-02898 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA025224 (U.S. NIH Grant/Contract); CDR0000067033; 97-24-51 (Other Identifier: North Central Cancer Treatment Group); NCCTG-97-24-51 (Other Identifier: CTEP)