Clinical trial NCT00551369: Stereotactic Body Radiation Therapy in Treating Patients With Stage I or Stage II Non-Small Cell Lung Cancer That Can Be Removed By Surgery
Official title: A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients With Operable Stage I/II Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
stage II non-small cell lung cancer
adenocarcinoma of the lung
large cell lung cancer
squamous cell lung cancer
adenosquamous cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2007-10-31
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Stereotactic body radiation therapy may be able to send x-rays directly to the tumor and cause less damage to normal tissue near the tumor.

PURPOSE: This phase II trial is studying how well stereotactic body radiation therapy works in treating patients with stage I or stage II non-small cell lung cancer that can be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* Determine whether treatment with radiotherapy involving a high biological dose with limited treatment volume (using stereotactic body radiotherapy \[SBRT\] techniques) achieves acceptable primary tumor control (i.e., ≥ 90% at 2 years) in patients with resectable early-stage non-small cell lung cancer.

Secondary

* Determine whether treatment with radiotherapy involving a high biological dose with limited treatment volume (using SBRT techniques) achieves acceptable treatment-related toxicity.
* Estimate the disease-free survival and the overall survival rate at 2 years.
* Observe patterns of failure in the first 2 years.
* Assess the level of comorbidity burden on morbidity and efficacy.
* Determine if blood markers prior to, during the course of treatment (between the second and the last dose of SBRT), and at the first follow-up after SBRT predict 2-year primary tumor control and predict for grade ≥ 2 treatment-related toxicities

OUTLINE: This is a multicenter study.

Patients receive 3 fractions of stereotactic body radiotherapy over 14 days. Patients with disease progression undergo surgical resection as salvage local therapy.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer, including any of the following primary tumor types:

  * Squamous cell carcinoma
  * Adenocarcinoma
  * Large cell carcinoma
  * Large cell neuroendocrine tumor
  * Non-small cell carcinoma not otherwise specified
* No pure type bronchoalveolar cell carcinoma
* Stage I or II disease based on 1 of the following combinations of primary tumor, regional nodes, metastasis (TNM) staging:

  * T1, N0, M0
  * T2 (≤ 5 cm), N0, M0
  * T3 (≤ 5 cm), N0, M0 (chest wall primary tumors only)
* No T2 or T3 primary tumors \> 5 cm or T3 primary tumors involving the central chest and structures of the mediastinum
* No primary tumor of any T-stage within or touching the zone of the proximal bronchial tree, defined as a volume of 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, or right and left lower lobe bronchi)
* Patients with hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan will be considered N0

  * Patients with \> 1 cm hilar or mediastinal lymph nodes on CT scan OR abnormal PET scan (including suspicious but nondiagnostic uptake) will still be eligible if directed tissue biopsies of all abnormally identified areas are negative for cancer
* No direct evidence of regional or distant metastases after appropriate staging studies
* Considered a reasonable candidate for surgical resection of the primary tumor, according to the following criteria:

  * Primary tumor predicted to be technically resectable with a high likelihood of negative surgical margins (as determined by a qualified thoracic surgeon)
  * Baseline forced expiratory volume (FEV)_1 \> 35% predicted
  * Postoperative predicted FEV_1 \> 30% predicted
  * Diffusion capacity \> 35% predicted
  * No hypoxemia (e.g., partial pressure of arterial oxygen (PaO2) of ≤ 60 mm Hg) and/or hypercapnia (e.g., partial pressure of arterial carbon dioxide (PaCO2) \> 50 mm Hg) at baseline
  * No severe pulmonary hypertension
  * No severe cerebral, cardiac, or peripheral vascular disease
  * No severe chronic heart disease
* Pleural effusion, if present, must be deemed too small to tap under CT scan guidance and must not be evident on chest x-ray

  * Pleural effusion that appears on chest x-ray will be allowed only after thoracotomy or other invasive procedure

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-1
* Absolute neutrophil count ≥ 1,800/mm³
* Platelet count ≥ 100,000/mm\^3
* Hemoglobin ≥ 8.0 g/dL (transfusion allowed)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No synchronous primary or other invasive malignancy within the past 3 years other than nonmelanoma skin cancer or in situ cancer
* No active systemic, pulmonary, or pericardial infection
* No weight loss \> 5% for any reason within the past 3 months

PRIOR CONCURRENT THERAPY:

* No prior radiotherapy for lung cancer

  * Prior radiotherapy as part of treatment for head and neck cancer, breast cancer, or other non-lung cancer is allowed provided there will not be significant overlap with the stereotactic body radiotherapy fields
* No prior chemotherapy or surgical resection for this lung cancer
* No other concurrent local or regional antineoplastic therapy (including standard fractionated radiotherapy, non-approved systemic therapy, and surgery), except at disease progression

Primary outcomes:
measure: Primary Tumor Control at 2 Years
timeFrame: From start of treatment to 2 years.
Secondary outcomes:
measure: Rate of Treatment-related Grade 3 or 4 Toxicity
timeFrame: From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis.
measure: Other Grade 3-5 Adverse Events
timeFrame: From start of treatment to end of follow-up. Analysis can occur at or after time of primary outcome measure analysis.
measure: Primary Tumor Failure (PTF), Marginal Failure (MF), Regional Failure (RF), Metastatic Dissemination (MD), Disease-free Survival (DFS), and Overall Survival (OS) at 2 Years
timeFrame: From start of treatment to 2 years.
measure: Level of Comorbidity Burden on Morbidity and Efficacy
timeFrame: From start of treatment to end of follow-up.
measure: Assessment of Predictive Value of Blood Markers for Primary Tumor Control at 2 Years and Treatment-related Adverse Events ≥ Grade 2
timeFrame: From start of treatment to 2 years.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Berkeley
country: United States
facility: Alta Bates Summit Comprehensive Cancer Center
state: California
city: Carmichael
country: United States
facility: Mercy Cancer Center at Mercy San Juan Medical Center
state: California
city: Greenbrae
country: United States
facility: Marin Cancer Institute at Marin General Hospital
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
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: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Grand Rapids
country: United States
facility: Lacks Cancer Center at Saint Mary's Health Care
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital - Royal Oak Campus
state: Michigan
city: Saint Louis
country: United States
facility: Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
state: Missouri
city: New York
country: United States
facility: NYU Cancer Institute at New York University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Cancer Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Hershey
country: United States
facility: Penn State Cancer Institute at Milton S. Hershey Medical Center
state: Pennsylvania
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Alexandria
country: United States
facility: INOVA Alexandria Hospital
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
Study officials:
affiliation: Simmons Cancer Center
name: Robert D. Timmerman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical College of Wisconsin
name: Elizabeth M. Gore, MD
role: STUDY_CHAIR
affiliation: NYU Langone Health
name: Harvey I. Pass, MD
role: STUDY_CHAIR
affiliation: University of Maryland Greenebaum Cancer Center
name: Martin J. Edelman, MD
role: STUDY_CHAIR
References:
citation: Timmerman RD, Paulus R, Pass HI, Gore EM, Edelman MJ, Galvin J, Straube WL, Nedzi LA, McGarry RC, Robinson CG, Schiff PB, Chang G, Loo BW Jr, Bradley JD, Choy H. Stereotactic Body Radiation Therapy for Operable Early-Stage Lung Cancer: Findings From the NRG Oncology RTOG 0618 Trial. JAMA Oncol. 2018 Sep 1;4(9):1263-1266. doi: 10.1001/jamaoncol.2018.1251.