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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00003869
First received: November 1, 1999
Last updated: May 2, 2014
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Stage IIIA Non-small Cell Lung Cancer
Stage IIIB Non-small Cell Lung Cancer
Stage IV Non-small Cell Lung Cancer
Drug: carboxyamidotriazole
Other: placebo
Procedure: quality-of-life assessment
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Phase III Randomized, Double-Blind Study of CAI and Placebo in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Participants With Severe Non-hematologic Adverse Events [ Time Frame: every cycle during treatment ] [ Designated as safety issue: Yes ]
    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)

  • Time to Disease Progression (TTP) [ Time Frame: up to 5 years ] [ Designated as safety issue: No ]

    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)


  • Clinically Significant (10-point) Decrease in UNISCALE Quality of Life (QOL)Assessment From Baseline to Week 8 [ Time Frame: Baseline to week 8 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • Number of Patients With a Confirmed Tumor Responses Treated With CAI. [ Time Frame: During Treatment (up to 5 years) ] [ Designated as safety issue: No ]

    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).


Enrollment: 186
Study Start Date: April 1999
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (CAI)
Patients receive oral carboxyamidotriazole daily.
Drug: carboxyamidotriazole
Given PO
Other Names:
  • CAI
  • carboxyamido-triazole
  • carboxyaminoimidazole
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive oral placebo daily
Other: placebo
Given PO
Other Name: PLCB
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003869

Locations
United States, Minnesota
North Central Cancer Treatment Group
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Edith Perez North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00003869     History of Changes
Other Study ID Numbers: NCI-2012-02898, NCI-2012-02898, CDR0000067033, 97-24-51, NCCTG-97-24-51, U10CA025224
Study First Received: November 1, 1999
Results First Received: November 24, 2010
Last Updated: May 2, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboxyamido-triazole
Antineoplastic Agents
Calcium Channel Blockers
Cardiovascular Agents
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014