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Completed

NCT Number: NCT00003869

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

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.

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Key information

Conditions

Stage IIIA Non-Small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Stage IIIB Non-small Cell Lung Cancer Stage IV Non-small Cell Lung Cancer Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

North Central Cancer Treatment Group

Rochester, Minnesota, 55905, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

carboxyamidotriazole

Drug

Given PO

Other names: CAI, carboxyamido-triazole, carboxyaminoimidazole

Placebo

Other

Given PO

Other names: PLCB

quality-of-life assessment

Procedure

Ancillary studies

Other names: quality of life assessment

laboratory biomarker analysis

Other

Correlative studies

Primary outcomes

  1. Overall Survival (OS)

    Time frame: up to 5 years

    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.

Secondary outcomes

  1. Participants With Severe Non-hematologic Adverse Events

    Time frame: every cycle during treatment

    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)

  2. Time to Disease Progression (TTP)

    Time frame: up to 5 years

    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)

  3. Clinically Significant (10-point) Decrease in UNISCALE Quality of Life (QOL)Assessment From Baseline to Week 8

    Time frame: 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.

  4. 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

    Time frame: 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.

  5. Number of Patients With a Confirmed Tumor Responses Treated With CAI.

    Time frame: During Treatment (up to 5 years)

    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).

Sponsors and collaborators

Lead sponsor

National Cancer Institute (NCI)

Nih

Registry information

Official study title

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

Important dates

Study start
1999
Primary completion
2008
Study completion
2008
First posted
Jan 27, 2003
Registry last updated
May 20, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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