Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer

NCT00960999 | Completed Phase 2 Results DMC

• 2 other identifiers: RTOG-0915CDR0000652101
• Study Type: interventional
• Target: 94
• Locations: 2 countries
• Sites: 38

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.

Conditions

Lung Cancer

Keywords

stage I non-small cell lung cancer; squamous cell lung cancer; adenocarcinoma of the lung; large cell lung cancer

Outcome Measures

Primary Outcomes (1)

• 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)

  Number of patients with ≥ grade 3 AE occurring within 1 year of treatment (TRT) start and reported as DPPRT among this subset of CTCAE v4: pericardial effusion, pericarditis, restrictive cardiomyopathy, dysphagia, esophagitis, esophageal fistula/obstruction/perforation/stenosis/ulcer/hemorrhage, rib fracture, brachial plexopathy, recurrent laryngeal nerve palsy, myelitis, atelectasis, bronchopulmonary/mediastinal/pleural/tracheal hemorrhage, bronchial/pulmonary/bronchopleural/tracheal fistula, hypoxia, bronchial/tracheal obstruction, pleural effusion, pneumonitis, pulmonary fibrosis, skin ulceration (thorax only), FEV1 (Forced Expiratory Volume) or FVC (forced vital capacity) decline, or grade 5 related to TRT. Each arm is considered independently. For each arm, \>=5 of 38 analyzable subjects experiencing a grade ≥ 3 AE during the 1st year following TRT start would determine the respective TRT excessively toxic. For each arm this design provides 88% power with a 0.10 type I error rate.

  From start of treatment to 1 year

Secondary Outcomes (11)

• 1-year Primary Tumor Control Rate

  From start of treatment to 1 year

• 1-year Overall Survival Rate

  From start of treatment to 1 year

• 1-year Disease-free Survival Rate

  From start of treatment to 1 year

• Change in Peak Standardized Uptake Value (SUV) at 12 Weeks Post-radiotherapy

  Baseline and 12 weeks post-radiotherapy

• Change in Peak Standardized Uptake Value (SUV) at One Year Post-radiotherapy

  Baseline and one year

Study Arms (2)

Single-fraction SBRT (34 Gy)

EXPERIMENTAL

Single-fraction stereotactic body radiation therapy (SBRT) of 34 Gy

Radiation: Single-fraction stereotactic body radiation therapy (SBRT)

Multiple-fraction SBRT (48 Gy)

EXPERIMENTAL

Multiple-fraction stereotactic body radiation therapy (SBRT) given in four daily 12 Gy fractions for a total dose of 48 Gy

Radiation: Multiple-fraction stereotactic body radiation therapy (SBRT)

Interventions

Single-fraction stereotactic body radiation therapy (SBRT) RADIATION

34 Gy in 1 fraction to the prescription line at the edge of the planning target volume (PTV). The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and \< 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least \< 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be \< 10%.

Single-fraction SBRT (34 Gy)

Multiple-fraction stereotactic body radiation therapy (SBRT) RADIATION

48 Gy in four 12 Gy fractions to the prescription line at the edge of the planning target volume (PTV). Treatments are given on 4 consecutive calendar days, but at least 18 hours apart. The maximum dose must exist within the PTV, and the prescription isodose surface must be ≥ 60% and \< 90% of the maximum dose. 99% of the PTV must receive a minimum of 90% of the prescription dose. The maximum dose to any point ≥ 2 cm away from the PTV in any direction must be at least \< 50% of the prescription dose. The percent of the lungs (excluding PTV) receiving 20 Gy or more must be \< 10%.

Multiple-fraction SBRT (48 Gy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Stage T1, N0, M0 or T2 (≤ 5 cm), N0, M0, (AJCC Staging, 6th Ed.), based upon #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.
• 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.
• 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;

You may not qualify if:

• Patients with T2 primary tumors \> 5 cm or involving the central plural and/or structures of the mediastinum;
• 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);
• 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;
• Previous radiotherapy to the lung or mediastinum;
• 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.
• Previous surgery for this lung or mediastinum tumor;
• 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;
• Patients with active systemic, pulmonary, or pericardial infection;
• Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator
• NRG Oncology: collaborator

Study Sites (38)

Auburn Radiation Oncology

Auburn, California, 95603, United States

Location

Alta Bates Summit Comprehensive Cancer Center

Berkeley, California, 94704, United States

Location

Radiation Oncology Centers - Cameron Park

Cameron Park, California, 95682, United States

Location

Mercy Cancer Center at Mercy San Juan Medical Center

Carmichael, California, 95608, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

University of Colorado Cancer Center at UC Health Sciences Center

Aurora, Colorado, 80045, United States

Location

Baptist Cancer Institute - Jacksonville

Jacksonville, Florida, 32207, United States

Location

M.D. Anderson Cancer Center at Orlando

Orlando, Florida, 32806, United States

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Chicago, Illinois, 60611-3013, United States

Location

Community Cancer Center

Normal, Illinois, 61761, United States

Location

Advocate Lutheran General Cancer Care Center

Park Ridge, Illinois, 60068-1174, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Parkview Regional Cancer Center at Parkview Health

Fort Wayne, Indiana, 46805, United States

Location

Memorial Hospital of South Bend

South Bend, Indiana, 46601, United States

Location

Lucille P. Markey Cancer Center at University of Kentucky

Lexington, Kentucky, 40536-0093, United States

Location

James Graham Brown Cancer Center at University of Louisville

Louisville, Kentucky, 40202, United States

Location

Josephine Ford Cancer Center at Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Great Lakes Cancer Institute at McLaren Regional Medical Center

Flint, Michigan, 48532, United States

Location

CCOP - Kansas City

Kansas City, Missouri, 64131, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263-0001, United States

Location

James P. Wilmot Cancer Center at University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Stony Brook University Cancer Center

Stony Brook, New York, 11794-9446, United States

Location

Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Flower Hospital Cancer Center

Sylvania, Ohio, 43560, United States

Location

Providence Cancer Center at Providence Portland Medical Center

Portland, Oregon, 97213-2967, United States

Location

Geisinger Cancer Institute at Geisinger Health

Danville, Pennsylvania, 17822-0001, United States

Location

Dale and Frances Hughes Cancer Center at Pocono Medical Center

East Stroudsburg, Pennsylvania, 18301, United States

Location

Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033-0850, United States

Location

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

Location

INOVA Alexandria Hospital

Alexandria, Virginia, 22304, United States

Location

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298-0037, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, 53295, United States

Location

Grand River Regional Cancer Centre at Grand River Hospital

Kitchener, Ontario, N2G 1G3, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

McGill Cancer Centre at McGill University

Montreal, Quebec, H2W 1S6, Canada

Location

Related Publications (1)

• 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.

  PMID: 26530743 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: NRG Oncology

seiferheldw@nrgoncology.org

Study Officials

• Gregory Videtic, MD

  The Cleveland Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 16, 2009
• First Posted: August 18, 2009
• Study Start: November 1, 2009
• Primary Completion: August 1, 2012
• Study Completion: May 14, 2018
• Last Updated: March 4, 2020
• Results First Posted: November 4, 2014

Record last verified: 2020-02

Locations

US (35); CA (3)