Lung Cancer
Conditions
Keywords
stage I non-small cell lung cancer
Brief summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. It is not yet known if selenium is effective in preventing the growth of new tumors in patients with previously resected non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying selenium to see how well it works compared to a placebo in preventing the development of second primary lung tumors in patients who have undergone surgery to remove stage I non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary Objective: * Determine the efficacy of selenium in terms of reducing the incidence of second primary lung tumors in participants with previously resected stage I non-small cell lung cancer. Secondary Objectives: * Evaluate the qualitative and quantitative toxicity of selenium in these patients. * Compare the incidence of specific cancers, mortality from cancer, and overall survival of participants treated with selenium vs those treated with placebo. OUTLINE: This is a randomized, double-blinded, placebo-controlled, multicenter study. Participants are stratified according to smoking status (actively smoking or stopped less than 1 year ago vs. stopped at least 1 year ago vs. never smoked or no more than 100 cigarettes ever), gender, and stage and previous therapy (stage IA vs. stage IB with previous therapy vs. stage IB with no previous therapy). Participants are randomized in a 1:2 ratio to arm I and arm II. * Arm I: Participants receive an oral yeast placebo as in arm II. * Arm II: Participants receive oral selenium yeast daily for 6 months. Treatment repeats every 6 months for 8 courses for a total of 4 years in the absence of unacceptable toxicity. Participants are followed annually (every 12 months) for 10 years. PROJECTED ACCRUAL: A total of 1,960 participants will be accrued for this study within 4 years.
Interventions
OTHERplacebo
Given orally
DRUGselenium
Given orally
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
North Central Cancer Treatment Group
NCIC Clinical Trials Group
Cancer and Leukemia Group B
ECOG-ACRIN Cancer Research Group
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
RUN-IN PERIOD: Inclusion Criteria: * Histologically confirmed, completely resected stage IA (pT1, N0) or IB (pT2, N0) non-small lung cancer (except carcinoid)\* * Completion of treatment for stage I lung cancer within the past 6 to 36 months and currently disease free * At least one mediastinal lymph node sampled at resection NOTE: \*Southwest Oncology Group (SWOG) and Cancer and Leukemia Group B (CALGB) patients must be T1, N0; CALGB patients may be T2, N0 provided disease was completely resected prior to June 1, 2001 and participation in CALGB 9633 was refused if offered * 18 years old and over * Eastern Cooperative Oncology Group performance status 0-1 * Bilirubin no greater than upper limit of normal (ULN) * Serum glutamic-oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) no greater than ULN * Prior mineral, herbal, phytochemical, or vitamin supplementation allowed * Concurrent non-selenium containing mineral, herbal, phytochemical, or vitamin supplementation allowed if schedule and supplementation prior to study remains unchanged
Exclusion criteria
* Evidence of new or recurrent lung cancer on chest x-ray within the past 8 weeks * Synchronous lung or non-lung lesions or metastasis, even if resectable * History of more than one primary lung cancer at any time * Concurrent or other prior cancer within the past 5 years except localized non-melanoma skin cancer * Prior or concurrent chemotherapy for recurrent lung cancer * Prior or concurrent radiotherapy for recurrent lung cancer * Concurrent surgery * Concurrent supplement(s) containing more than 50 micrograms of selenium STUDY PHASE: * Free of disease * Consumed at least 75% of tablets during 4-week run-in period
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Second Primary Lung Tumor | Assessed annually for 10 years after randomization | Incidence rate of second primary lung tumor was defined as the number of new second primary lung tumors per 100 population at risk in a year. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 5-year Progression-free Survival Rate | Assessed annually for 5 years after randomization | Progression-Free Survival (PFS) was defined as the time from randomization to second primary lung cancer or recurrence. Cases without events have been censored at the time of last known alive. Kaplan-Meier method was used to estimate 5-year PFS rate. Accurate determination of whether a cancer occurrence is recurrence or whether it is a second primary is critical. All suspicious lesions identified clinically and/or radiographically were verified histologically. Patients with at least one of the following is considered as having second primary lung cancer. 1. Different histologic type 2. Location in different lobe 3. Location in contralateral lung 4. Occurrence \> 5 years after initial diagnosis |
| 5-year Overall Survival Rate | Assessed annually for 5 years after randomization | Overall survival (OS) was defined as the time from randomization to death due to any cause. Cases without death had been censored at the time of last known alive. Kaplan-Meier method was used to estimate 5-year OS rate. |
Countries
Canada, United States
Participant flow
Recruitment details
The study was activated on 10/6/2000, accrued its first patient on 12/18/2000, and terminated early on 11/5/2009 due to futility analysis with a total accrual of 1772 patients to step 1. Of the 1772 patients, 1561 were randomized on step 2.
Pre-assignment details
The study had a 4-week run-in period to select patients with good compliance with the protocol therapy, defined as consuming at least 75% of prescribed placebo tablets. These patients were then randomized.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Placebo) Participants receive an oral yeast placebo as in arm II.
placebo: Given orally | 521 |
| Arm II (Selenium) Participants receive oral selenium yeast daily for 6 months. Treatment repeats every 6 months for 8 courses for a total of 4 years in the absence of unacceptable toxicity.
selenium: Given orally | 1,040 |
| Total | 1,561 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 20 |
| Overall Study | Death | 12 | 18 |
| Overall Study | Maximum dose reached | 0 | 2 |
| Overall Study | Not start protocol therapy | 44 | 175 |
| Overall Study | Off treatment reasons not reported | 79 | 70 |
| Overall Study | Other | 105 | 212 |
| Overall Study | Other complicating disease | 17 | 30 |
| Overall Study | Progressive disease | 52 | 117 |
| Overall Study | Start non-protocol therapy | 3 | 1 |
| Overall Study | Withdrawal by Subject | 67 | 157 |
Baseline characteristics
| Characteristic | Arm I (Placebo) | Arm II (Selenium) | Total |
|---|---|---|---|
| Age, Continuous | 66 Years | 66 Years | 66 Years |
| Sex: Female, Male Female | 271 Participants | 531 Participants | 802 Participants |
| Sex: Female, Male Male | 250 Participants | 509 Participants | 759 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 55 / 477 | 99 / 865 |
| serious Total, serious adverse events | 9 / 477 | 13 / 865 |
Outcome results
Primary
Incidence Rate of Second Primary Lung Tumor
Incidence rate of second primary lung tumor was defined as the number of new second primary lung tumors per 100 population at risk in a year.
Time frame: Assessed annually for 10 years after randomization
Population: all randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Placebo) | Incidence Rate of Second Primary Lung Tumor | 1.30 cases/100 person years |
| Arm II (Selenium) | Incidence Rate of Second Primary Lung Tumor | 1.62 cases/100 person years |
p-value: 0.29495% CI: [0.64, 2.37]Log Rank
Secondary
5-year Overall Survival Rate
Overall survival (OS) was defined as the time from randomization to death due to any cause. Cases without death had been censored at the time of last known alive. Kaplan-Meier method was used to estimate 5-year OS rate.
Time frame: Assessed annually for 5 years after randomization
Population: All randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Placebo) | 5-year Overall Survival Rate | 0.799 proportion of participants |
| Arm II (Selenium) | 5-year Overall Survival Rate | 0.768 proportion of participants |
p-value: 0.154Log Rank
Secondary
5-year Progression-free Survival Rate
Progression-Free Survival (PFS) was defined as the time from randomization to second primary lung cancer or recurrence. Cases without events have been censored at the time of last known alive. Kaplan-Meier method was used to estimate 5-year PFS rate. Accurate determination of whether a cancer occurrence is recurrence or whether it is a second primary is critical. All suspicious lesions identified clinically and/or radiographically were verified histologically. Patients with at least one of the following is considered as having second primary lung cancer. 1. Different histologic type 2. Location in different lobe 3. Location in contralateral lung 4. Occurrence \> 5 years after initial diagnosis
Time frame: Assessed annually for 5 years after randomization
Population: All randomized patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Placebo) | 5-year Progression-free Survival Rate | 0.796 proportion of participants |
| Arm II (Selenium) | 5-year Progression-free Survival Rate | 0.744 proportion of participants |
p-value: 0.069Log Rank