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.

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.

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