Stage IIIA Non-small Cell Lung CancerPhase 3NCT00003869
Carboxyamidotriazole in Treating Patients With Stage III or Stage IV Non-small Cell Lung Cancer
A Phase 3 study testing carboxyamidotriazole, quality-of-life assessment and laboratory biomarker analysis in people with Stage IIIA Non-small Cell Lung Cancer and Stage IIIB Non-small Cell Lung Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- What is being tested?
- carboxyamidotriazole, quality-of-life assessment and laboratory biomarker analysis
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 186 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 1999to May 2008
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 29Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
North Central Cancer Treatment Group
Rochester, Minnesota, 55905
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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:
- 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.
- Conditions
- Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Being tested
- carboxyamidotriazole, placebo, quality-of-life assessment, laboratory biomarker analysis
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carboxyamidotriazoleDrug
Also called CAI, carboxyamido-triazole, carboxyaminoimidazole
Given PO
placeboOther
Also called PLCB
Given PO
quality-of-life assessmentProcedure or surgery
Also called quality of life assessment
Ancillary studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Arm I (CAI) | Experimental | Patients receive oral carboxyamidotriazole daily. Receives: Drug: carboxyamidotriazole; Procedure: quality-of-life assessment; Other: laboratory biomarker analysis |
| Arm II (placebo) | Placebo comparator | Patients receive oral placebo daily Receives: Other: placebo; Procedure: quality-of-life assessment; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 5 years
Secondary outcomes (5)
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)
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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).
Measured: During Treatment (up to 5 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startApr 1999
- Primary completionMay 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Stage IIIA Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 186 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Edith Perez, Principal investigator, North Central Cancer Treatment Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00003869
- Sponsor's protocol ID
- NCI-2012-02898
- Other IDs
- NCI-2012-02898, CDR0000067033, 97-24-51, NCCTG-97-24-51, U10CA025224
- Status last verified
- Dec 2012
- First submitted
- 1 Nov 1999
- Last updated
- 20 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Randomized, Double-Blind Study of CAI and Placebo in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT00003869
- Acronym / sponsor ID
- NCI-2012-02898
- Conditions
- Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer, Stage IV Non-small Cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 186 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Apr 1999
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Posted 22 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (CAI) | Experimental | Drug: carboxyamidotriazole, Procedure: quality-of-life assessment, Other: laboratory biomarker analysisPatients receive oral carboxyamidotriazole daily. |
| Arm II (placebo) | Placebo comparator | Other: placebo, Procedure: quality-of-life assessment, Other: laboratory biomarker analysisPatients receive oral placebo daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (29 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carboxyamidotriazoleAlso: CAI, carboxyamido-triazole, carboxyaminoimidazoleGiven PO | Drug | Arm I (CAI) |
| placeboAlso: PLCBGiven PO | Other | Arm II (placebo) |
| quality-of-life assessmentAlso: quality of life assessmentAncillary studies | Procedure or surgery | Arm I (CAI), Arm II (placebo) |
| laboratory biomarker analysisCorrelative studies | Other | Arm I (CAI), Arm II (placebo) |
Primary outcome
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.
5 secondary outcomes
Participants With Severe Non-hematologic Adverse Events
Time frame: every cycle during treatment
Time to Disease Progression (TTP)
Time frame: up to 5 years
Clinically Significant (10-point) Decrease in UNISCALE Quality of Life (QOL)Assessment From Baseline to Week 8
Time frame: 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
Time frame: Baseline to week 8
Number of Patients With a Confirmed Tumor Responses Treated With CAI.
Time frame: During Treatment (up to 5 years)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edith Perez principal investigator
North Central Cancer Treatment Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing carboxyamidotriazole, quality-of-life assessment and laboratory biomarker analysis in people with Stage IIIA Non-small Cell Lung Cancer and Stage IIIB Non-small Cell Lung Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) (time frame: up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2014.