Lung Cancer
Conditions
Keywords
stage IV non-small cell lung cancer, adenosquamous cell lung cancer, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer
Brief summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Sometimes, after chemotherapy, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether radiation therapy is more effective than observation after chemotherapy in treating non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying how well radiation therapy works compared with observation after chemotherapy in treating patients with stage IV non-small cell lung cancer.
Detailed description
OBJECTIVES: Primary * To assess whether the addition of radiotherapy to radiographically apparent residual disease after an initial course of standard chemotherapy results in an improvement in overall survival of patients with oligometastatic stage IV non-small cell lung cancer. Secondary * To compare the progression-free survival of patients treated with radiotherapy vs observation after standard chemotherapy. * To compare the time to disease progression and time to treatment failure in these patients. * To compare the confirmed response rate in these patients. * To compare the duration of response in these patients. * To compare the adverse events in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to prior treatment with bevacizumab during first-line chemotherapy (yes vs no), number of standard chemotherapy courses (2-3 vs 4-6), Linear Analog Self Assessment value (≤ 7 vs \> 7), and histology (predominantly squamous cell vs not predominantly squamous cell). Patients are randomized to 1 of 2 treatment arms. * Arm I: Patients undergo observation for 6 weeks. * Arm II: Patients undergo radiotherapy 5 days a week for 6 weeks to all sites of gross disease. After completion of study therapy, patients are followed every 3-6 months for up to 5 years.
Interventions
OTHERclinical observation
Patients undergo observation for 6 weeks.
RADIATIONradiation therapy
Patients undergo radiotherapy 5 days a week for 6 weeks.
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) * Mixed histology allowed if all components are consistent with NSCLC * Squamous cell histology allowed * Stage IV disease * Oligometastatic disease (M1 with 1-3 metastases) * Patients with M1 disease that involves intrapulmonary metastases are eligible provided ≤ 40% of the total lung volume receives ≥ 20 Gy of radiotherapy * Previously untreated disease OR achieved stable disease or partial response within 8 weeks after completion of 2-6 courses of standard platinum-based chemotherapy (administered every 3-4 weeks) * Pleural effusion allowed provided it is minimal * No history of or current brain metastases * Patients who have had up to 3 brain metastases allowed provided they have been treated with not signs of progression PATIENT CHARACTERISTICS: * ECOG performance status 0-1 * Life expectancy ≥ 12 weeks * Platelet count ≥ 100,00/mm\^3 * Hemoglobin ≥ 9 g/dL * WBC ≥ 2,000/mm\^3 * Creatinine ≤ 2 times upper limit of normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Able to undergo radiotherapy, based on radiation oncology consultation * Willing and able to comply with study treatment * FEV\_1 ≥ 1 L * No requirement for daily supplemental oxygen * No second primary malignancy, except for any of the following: * Carcinoma in situ of the cervix * Nonmelanoma skin cancer * History of low-grade (Gleason score ≤ 6) localized prostate cancer, even if diagnosed within the past 5 years * Stage I breast cancer that was treated within the past 5 years * Other malignancy that was diagnosed and definitely treated ≥ 5 years ago with no subsequent evidence of recurrence * No concurrent severe and/or uncontrolled medical condition, including any of the following: * Angina pectoris * Congestive heart failure within the past 3 months, unless LVEF \> 40% * Myocardial infarction within the past 6 months * Cardiac arrhythmia * No clinically significant infection * No psychiatric illness or social situation that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: * See Disease Characteristics * No prior therapy for this cancer other than 2-6 courses of standard platinum-based chemotherapy with or without bevacizumab * No prior radiotherapy to the treatment sites (e.g., primary lesion, clinically involved nodes, or metastatic lesions) * No bevacizumab during and for 4 weeks after completion of radiotherapy * No concurrent systemic chemotherapy * No other maintenance systemic therapy during radiotherapy * No other concurrent investigational agents for the primary neoplasm * No concurrent intensity modulated radiotherapy * No concurrent prophylactic nodal radiotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Time from registration to death or last follow-up (up to 5 years) | Overall survival was defined as the time from registration to the date of death or last follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | Up to 5 years | A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations around 3 months apart. All participants with measurable disease (non-CR at baseline, etc.), meeting the eligibility criteria who have signed a consent form and have started the study were evaluable for response. |
| Progression-free Survival | Time from registration to disease progression or death (up to 5 years) | Progression-free survival was defined as the time from randomization to the first of either death due to any cause or progression. |
| Time to Disease Progression | Time from registration to disease progression (up to 5 years) | Time to disease progression was defined as the time from randomization to the earliest date documentation of disease progression occurs. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. |
| Time to Treatment Failure | Up to 5 years | Time to treatment failure was defined as the time from the date of randomization to the date at which the patient was removed from treatment (Arm II) or no treatment (Arm I) due to progression, adverse events, or refusal. |
| Duration of Response | Up to 5 years | Duration of response was defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status was first noted to be either a complete response (CR) or partial response (PR) to the earliest date progression was documented. |
Countries
United States
Participant flow
Recruitment details
Four participants were pre-registered between May 2009 and March 2010. One participant was deemed a screen failure due to eligibility reasons and 3 participants have been randomized between October 2009 and March 2010. The study was terminated prematurely on July 16, 2010 due to slow enrollment.
Pre-assignment details
One of the randomized participants was deemed a cancel after going off study prior to receiving study treatment, thus, excluded from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (No Radiation) Patients undergo observation for 6 weeks. | 1 |
| Arm II (Radiation Therapy) Patients undergo radiotherapy 5 days a week for 6 weeks to all sites of gross disease. | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease Progression | 1 | 0 |
Baseline characteristics
| Characteristic | Arm I (No Radiation) | Arm II (Radiation Therapy) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants |
| Gender Female | 0 Participants | 0 Participants | 0 Participants |
| Gender Male | 1 Participants | 1 Participants | 2 Participants |
| Region of Enrollment United States | 1 participants | 1 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 1 | 1 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Overall Survival
Overall survival was defined as the time from registration to the date of death or last follow-up
Time frame: Time from registration to death or last follow-up (up to 5 years)
Population: Study terminated prematurely. Planned analyses was not performed. The data collected was not summarized in the data table due to the protected health information would specifically identify the study participants.
Secondary
Duration of Response
Duration of response was defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status was first noted to be either a complete response (CR) or partial response (PR) to the earliest date progression was documented.
Time frame: Up to 5 years
Population: Study terminated prematurely. Planned analyses was not performed. The data collected was not summarized in the data table due to the protected health information would specifically identify the study participants.
Secondary
Progression-free Survival
Progression-free survival was defined as the time from randomization to the first of either death due to any cause or progression.
Time frame: Time from registration to disease progression or death (up to 5 years)
Population: Study terminated prematurely. Planned analyses was not performed. The data collected was not summarized in the data table due to the protected health information would specifically identify the study participants.
Secondary
Response Rate
A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations around 3 months apart. All participants with measurable disease (non-CR at baseline, etc.), meeting the eligibility criteria who have signed a consent form and have started the study were evaluable for response.
Time frame: Up to 5 years
Population: Study terminated prematurely. Planned analyses was not performed. The data collected was not summarized in the data table due to the protected health information would specifically identify the study participants.
Secondary
Time to Disease Progression
Time to disease progression was defined as the time from randomization to the earliest date documentation of disease progression occurs. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death.
Time frame: Time from registration to disease progression (up to 5 years)
Population: Study terminated prematurely. Planned analyses was not performed. The data collected was not summarized in the data table due to the protected health information would specifically identify the study participants.
Secondary
Time to Treatment Failure
Time to treatment failure was defined as the time from the date of randomization to the date at which the patient was removed from treatment (Arm II) or no treatment (Arm I) due to progression, adverse events, or refusal.
Time frame: Up to 5 years
Population: Study terminated prematurely. Planned analyses was not performed. The data collected was not summarized in the data table due to the protected health information would specifically identify the study participants.