Clinical trial NCT00960999: Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer
Official title: A Randomized Phase II Study Comparing 2 Stereotactic Body Radiation Therapy (SBRT) Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
squamous cell lung cancer
adenocarcinoma of the lung
large cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2009-08-18
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. It is not yet known which regimen of stereotactic body radiation therapy is more effective in treating patients with non-small cell lung cancer.

PURPOSE: This randomized phase II trial is studying the side effects of two radiation therapy regimens and to see how well they work in treating patients with stage I non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* To determine the 1-year rate of ≥ grade 3 adverse events that are definitely, probably, or possibly related to treatment with single fraction vs multiple fraction stereotactic body radiotherapy in medically inoperable patients with stage I peripheral non-small cell lung cancer.

Secondary

* To estimate the 1-year primary tumor control rate in these patients.
* To estimate the 1-year overall survival and disease-free survival rate of these patients.
* To assess FDG-PET (fluorodeoxyglucose - positron emission tomography) standardized uptake value changes as a measure of treatment response and outcomes.
* To determine pulmonary function changes by treatment arm and response.
* To determine the association between biomarkers and primary tumor control and/or ≥ grade 2 radiation pneumonitis.

OUTLINE: This is a multicenter study. Patients are stratified according to Zubrod performance status (0 vs 1 vs 2) and T stage (T1 vs T2). Patients are randomized to 1 of 2 treatment arms.

After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Eligibility criteria: Inclusion Criteria:

1. Histological confirmation (by biopsy or cytology) of non-small cell lung cancer (NSCLC) prior to treatment; the following primary cancer types are eligible: squamous cell carcinoma, adenocarcinoma, large cell carcinoma, large cell neuroendocrine, or non-small cell carcinoma not otherwise specified; Note: although bronchioloalveolar cell carcinoma is a subtype of NSCLC, patients with the pure type of this malignancy are excluded from this study because the spread of this cancer between adjacent airways is difficult to target on computed tomography (CT).
2. Stage T1, N0, M0 or T2 (≤ 5 cm), N0, M0, (AJCC Staging, 6th Ed.), based upon #3.
3. Minimum diagnostic workup:

   * History/physical examination, including weight and assessment of Zubrod performance status, within 4 weeks prior to registration;
   * Evaluation by an experienced thoracic cancer clinician (a thoracic surgeon, medical oncologist, radiation oncologist, or pulmonologist) within 8 weeks prior to registration;
   * CT scan with intravenous contrast (unless medically contraindicated) within 8 weeks prior to registration of the entirety of both lungs and the mediastinum, liver, and adrenal glands; the primary tumor dimension will be measured on the CT. Positron emission tomography (PET) evaluation of the liver and adrenal glands also is permitted. In addition, if the enrolling institution has a combined PET/CT scanner and both aspects are of diagnostic quality and read by a trained radiologist, the PET/CT will meet the staging requirements for both CT and PET.
   * Whole body or wide field FDG-PET within 8 weeks prior to registration with adequate visualization of the primary tumor and draining lymph node basins in the hilar and mediastinal regions and adrenal glands; in the event of lung consolidation, atelectasis, inflammation or other confounding features, PET-based imaging correlated with CT imaging will establish the maximal tumor dimensions. Standardized uptake value (SUV) must be measured on PET. To be included in this analysis, the patient's PET studies must be performed with a dedicated bismuth germanium oxide (BGO), lutetium oxyorthosilicate (LSO), or gadolinium oxyorthosilicate (GSO) PET or PET/CT scanner. PET scanners with sodium iodide (Nal) detectors are not acceptable. If the baseline PET study is performed at the treating institution (or its affiliated PET facility), it is recommended that the reassessment PET scans be performed at the same site.
   * Pulmonary function tests (PFTs): Routine spirometry, lung volumes, and diffusion capacity, within 8 weeks prior to registration; arterial blood gases are optional. Note: All patients enrolled in this study must have these pulmonary assessments whether or not the reason for their medical inoperability is pulmonary based, since the objective assessment of pulmonary factors is a component of the outcomes assessment for this study.
4. Patients with hilar or mediastinal lymph nodes ≤ 1cm and no abnormal hilar or mediastinal uptake on PET will be considered N0. Patients with \> 1 cm hilar or mediastinal lymph nodes on CT or abnormal PET (including suspicious but non-diagnostic uptake) may still be eligible if directed tissue biopsy of all abnormally identified areas are negative for cancer.
5. The patient's resectable NSCLC must be considered medically inoperable by an experienced thoracic cancer clinician (a thoracic surgeon, medical oncologist, radiation oncologist, or pulmonologist) or a standard lobectomy and mediastinal lymph node dissection/sampling procedure. The patient may have underlying physiological medical problems that would prohibit a surgery due to a low probability of tolerating general anesthesia, the operation, the postoperative recovery period, or the removal of adjacent functioning lung. These types of patients with severe underlying health problems are deemed "medically inoperable." Standard justification for deeming a patient medically inoperable based on pulmonary function for surgical resection of NSCLC may include any of the following:

   * Baseline forced expiratory volume in one second (FEV1) \< 40% predicted;
   * Postoperative FEV1 \< 30% predicted;
   * Severely reduced diffusion capacity;
   * Baseline hypoxemia and/or hypercapnia;
   * Exercise oxygen consumption \< 50% predicted;
   * Severe pulmonary hypertension;
   * Diabetes mellitus with severe end organ damage;
   * Severe cerebral, cardiac, or peripheral vascular disease;
   * Severe chronic heart disease. If the patient has resectable disease but declines surgery after consulting with a thoracic surgeon, he/she will be considered eligible.
6. The patient must have measurable disease.
7. Zubrod Performance Status 0-2;
8. Age ≥ 18;
9. Negative serum or urine pregnancy test within 72 hours prior to registration for women of childbearing potential;
10. Women of childbearing potential and male participants must agree to use a medically effective means of birth control, such as condom/diaphragm and spermicidal foam, intrauterine device (IUD), or prescription birth control pills, throughout their participation in the treatment phase of the study
11. The patient must provide study specific informed consent prior to study entry.

Exclusion Criteria:

1. Patients with T2 primary tumors \> 5 cm or involving the central plural and/or structures of the mediastinum;
2. The primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume 2 cm in all directions around the proximal bronchial tree (carina, right and left main bronchi, right and left upper lobe bronchi, intermedius bronchus, right middle lobe bronchus, lingular bronchus, right and left lower lobe bronchi);
3. Direct evidence of regional or distant metastases after appropriate staging studies, or synchronous primary malignancy or prior malignancy in the past 2 years except for invasive malignancy that has been treated definitively and the patient remains disease free for \> 3 years with life expectancy of \> 3 years or carcinoma in situ or early stage skin cancers that have been treated definitively;
4. Previous radiotherapy to the lung or mediastinum;
5. Previous chemotherapy for this lung or mediastinum tumor; chemotherapy for another invasive malignancy is permitted if it has been treated definitively and the patient has remained disease free for \> 3 years.
6. Previous surgery for this lung or mediastinum tumor;
7. Plans for the patient to receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery) while on this protocol except at disease progression;
8. Patients with active systemic, pulmonary, or pericardial infection;
9. Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.

Primary outcomes:
measure: Counts of ≥ Grade 3 Adverse Events (AE) Graded by CTCAE v4 (Common Terminology Criteria for Adverse Events) That Are Definitely, Probably, or Possibly Related to Treatment (DPPRT)
timeFrame: From start of treatment to 1 year
Secondary outcomes:
measure: 1-year Primary Tumor Control Rate
timeFrame: From start of treatment to 1 year
measure: 1-year Overall Survival Rate
timeFrame: From start of treatment to 1 year
measure: 1-year Disease-free Survival Rate
timeFrame: From start of treatment to 1 year
measure: Change in Peak Standardized Uptake Value (SUV) at 12 Weeks Post-radiotherapy
timeFrame: Baseline and 12 weeks post-radiotherapy
measure: Change in Peak Standardized Uptake Value (SUV) at One Year Post-radiotherapy
timeFrame: Baseline and one year
measure: Change in Normalized Standardized Uptake Value (SUV) at 12 Weeks
timeFrame: Baseline and 12 weeks
measure: Change in Normalized Standardized Uptake Value (SUV) at One Year
timeFrame: Baseline and one year
measure: Change in Percentage of Expected Forced Expiratory Volume in 1 Second (FEV1) by Best Observed Tumor Response at 6 Months Post-radiotherapy [Forced Expiratory Volume in 1 Second (FEV1)]
timeFrame: From start of treatment to 6 months post-radiotherapy
measure: Change in Percentage of Expected Carbon Monoxide Diffusing Capacity (DLCO) by Best Observed Tumor Response at 6 Months Post-radiotherapy
timeFrame: From start of treatment to 6 months post-radiotherapy
measure: Association Between Biomarkers and Primary Tumor Control Rate
timeFrame: From start of treatment to 1 year
measure: Association Between Biomarkers and Grade 2+ Radiation Pneumonitis
timeFrame: From start of treatment to 1 year
Other outcomes:
Locations:
city: Auburn
country: United States
facility: Auburn Radiation Oncology
state: California
city: Berkeley
country: United States
facility: Alta Bates Summit Comprehensive Cancer Center
state: California
city: Cameron Park
country: United States
facility: Radiation Oncology Centers - Cameron Park
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan Medical Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center at Orlando
state: Florida
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Cancer Care Center
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Fort Wayne
country: United States
facility: Parkview Regional Cancer Center at Parkview Health
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center at University of Louisville
state: Kentucky
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: Great Lakes Cancer Institute at McLaren Regional Medical Center
state: Michigan
city: Kansas City
country: United States
facility: CCOP - Kansas City
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Danville
country: United States
facility: Geisinger Cancer Institute at Geisinger Health
state: Pennsylvania
city: East Stroudsburg
country: United States
facility: Dale and Frances Hughes Cancer Center at Pocono Medical Center
state: Pennsylvania
city: Hershey
country: United States
facility: Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Alexandria
country: United States
facility: INOVA Alexandria Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
city: Kitchener
country: Canada
facility: Grand River Regional Cancer Centre at Grand River Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill Cancer Centre at McGill University
state: Quebec
Study officials:
affiliation: The Cleveland Clinic
name: Gregory Videtic, MD
role: STUDY_CHAIR
References:
citation: Videtic GM, Hu C, Singh AK, Chang JY, Parker W, Olivier KR, Schild SE, Komaki R, Urbanic JJ, Timmerman RD, Choy H. A Randomized Phase 2 Study Comparing 2 Stereotactic Body Radiation Therapy Schedules for Medically Inoperable Patients With Stage I Peripheral Non-Small Cell Lung Cancer: NRG Oncology RTOG 0915 (NCCTG N0927). Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):757-64. doi: 10.1016/j.ijrobp.2015.07.2260. Epub 2015 Jul 17.