Back to resultsCarboxyamidotriazole in Treating Patients With Stage III or Stage IV Non-small Cell Lung Cancer
Primary Purpose
Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
carboxyamidotriazole
placebo
quality-of-life assessment
laboratory biomarker analysis
Sponsored by
About this trial
This is an interventional treatment trial for Stage IIIA Non-small Cell Lung Cancer
Eligibility 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
Sites / Locations
- North Central Cancer Treatment Group
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Arm I (CAI)
Arm II (placebo)
Arm Description
Patients receive oral carboxyamidotriazole daily.
Patients receive oral placebo daily
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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)
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)
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.
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.
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).
Full Information
NCT ID
NCT00003869
First Posted
November 1, 1999
Last Updated
May 2, 2014
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00003869
Brief Title
Carboxyamidotriazole in Treating Patients With Stage III or Stage IV Non-small Cell Lung Cancer
Official Title
Phase III Randomized, Double-Blind Study of CAI and Placebo in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
April 1999 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
186 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (CAI)
Arm Type
Experimental
Arm Description
Patients receive oral carboxyamidotriazole daily.
Arm Title
Arm II (placebo)
Arm Type
Placebo Comparator
Arm Description
Patients receive oral placebo daily
Intervention Type
Drug
Intervention Name(s)
carboxyamidotriazole
Other Intervention Name(s)
CAI, carboxyamido-triazole, carboxyaminoimidazole
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
placebo
Other Intervention Name(s)
PLCB
Intervention Description
Given PO
Intervention Type
Procedure
Intervention Name(s)
quality-of-life assessment
Other Intervention Name(s)
quality of life assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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.
Time Frame
up to 5 years
Secondary Outcome Measure Information:
Title
Participants With Severe Non-hematologic Adverse Events
Description
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 Frame
every cycle during treatment
Title
Time to Disease Progression (TTP)
Description
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)
Time Frame
up to 5 years
Title
Clinically Significant (10-point) Decrease in UNISCALE Quality of Life (QOL)Assessment From Baseline to Week 8
Description
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.
Time Frame
Baseline to week 8
Title
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
Description
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.
Time Frame
Baseline to week 8
Title
Number of Patients With a Confirmed Tumor Responses Treated With CAI.
Description
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).
Time Frame
During Treatment (up to 5 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edith Perez
Organizational Affiliation
North Central Cancer Treatment Group
Official's Role
Principal Investigator
Facility Information:
Facility Name
North Central Cancer Treatment Group
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
12. IPD Sharing Statement
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Carboxyamidotriazole in Treating Patients With Stage III or Stage IV Non-small Cell Lung Cancer
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