Clinical trial NCT00750269: Stereotactic Body Radiation Therapy in Treating Patients With Stage I Non-Small Cell Lung Cancer
Official title: Seamless Phase I/II Study of Stereotactic Lung Radiotherapy (SBRT) for Early Stage, Centrally Located, Non-Small Cell Lung Cancer (NSCLC) in Medically Inoperable Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: stage I non-small cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: NRG Oncology
First posted: 2008-09-10
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
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.

PURPOSE: This phase I/II trial is studying the side effects and best dose of stereotactic body radiation therapy and to see how well it works in treating patients with stage I non-small cell lung cancer.

Detailed description: OBJECTIVES:

Primary

* To determine the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) in medically inoperable patients with centrally located stage I non-small cell lung cancer. (Phase I)
* To estimate the local control rate of SBRT at the MTD in these patients. (Phase II)

Secondary

* To estimate the rates of adverse events (other than dose-limiting toxicity) of ≥ grade 3 that is possibly, probably, or definitely related to treatment and that occurs within 1 year after the start of SBRT in these patients.
* To estimate the rates of late adverse events (i.e., occurs \> 1 year after the start of SBRT) in these patients.
* To estimate the local control and progression-free and overall survival rates in patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo stereotactic body radiotherapy every 2 days over 1½-2 weeks \[total of 5 fractions (FX)\] in the absence of disease progression or unacceptable toxicity.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  * Stage T1-2, N0, M0 disease

    * Tumor size ≤ 5 cm
    * Tumor must be 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 (i.e., 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) OR immediately adjacent to the mediastinal or pericardial pleura (PTV touching the pleura)
    * Hilar or mediastinal lymph nodes ≤ 1 cm AND no abnormal hilar or mediastinal uptake on positron emission tomography (PET) scan are considered N0

      * Mediastinal lymph node sampling by any technique is allowed but not required
      * Patients with \> 1 cm hilar or mediastinal lymph nodes on CT scan or abnormal PET scan (including suspicious but nondiagnostic uptake) are eligible provided directed tissue biopsies of all abnormally identified areas are negative for cancer
* Tumor deemed technically resectable, in the opinion of an experienced thoracic cancer surgeon, with a reasonable possibility of obtaining a gross total resection with negative margins, defined as a potentially curative resection (PCR)
* Patient deemed "medically inoperable" due to severe underlying physiological medical problems that would prohibit a PCR, including any of the following:

  * Baseline forced expiratory volume at 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-stage organ damage
  * Severe cerebral, cardiac, or peripheral vascular disease
  * Severe chronic heart disease
* Measurable disease as documented by CT scan or whole-body PET scan within the past 8 weeks

  * Patients with lesions that cannot be visualized by CT scan are not eligible
* Pleural effusion allowed provided it is deemed too small to tap under CT guidance and is not evident on chest x-ray

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

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-2
* Not pregnant
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 60 days after completion of study therapy
* No other invasive malignancy within the past 2 years except nonmelanomatous skin cancer or carcinoma in situ of the breast, oral cavity, or cervix

  * Prior lung cancer allowed provided the patient has been disease-free for ≥ 2 years

PRIOR CONCURRENT THERAPY:

* No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
* No prior chemotherapy for the study cancer
* No other concurrent local therapy (including standard-fractionated radiotherapy and/or surgery) or systemic therapy (including standard chemotherapy or biologic targeted agents) specifically intended as treatment for study cancer

  * Local or systemic therapy at the time of disease progression allowed

Primary outcomes:
measure: (Phase I) Maximum Tolerated Dose of Stereotactic Body Radiotherapy (SBRT) as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v4.0
timeFrame: From start of SBRT to 1 year
measure: (Phase II) Primary Tumor Control Rate at the Maximum Tolerated Dose (MTD)
timeFrame: From start of SBRT to 2 years.
Secondary outcomes:
measure: Progression-free Survival
timeFrame: From randomization to date of death, failure (local, regional or distant) or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.
measure: Overall Survival
timeFrame: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.
measure: Local Progression
timeFrame: From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months.
measure: Nodal Progression
timeFrame: From randomization to date of death, regional failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.
measure: Distant Metastases
timeFrame: From randomization to date of death, distant failure or last follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.
measure: Rate of Toxicity ≥ Grade 3 (Other Than DLT) Within One Year as Assessed by NCI CTCAE v4.0
timeFrame: From start of SBRT until 1 year.
measure: Rate of Late Toxicity (i.e., Occurs > 1 Year After the Start of SBRT) of ≥ Grade 3 as Assessed by NCI CTCAE v4.0
timeFrame: From start of treatment to end of follow-up. Analysis occurs after all patients have been potentially followed for 24 months, approximately 7.5 years from the start of the study.
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Arizona Center for Cancer Care - Peoria
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Burbank
country: United States
facility: Roy and Patricia Disney Family Cancer Center at Providence Saint Joseph Medical 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: Los Angeles
country: United States
facility: Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: New Britain
country: United States
facility: George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
state: Connecticut
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Baptist Cancer Institute - Jacksonville
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Orlando
country: United States
facility: M.D. Anderson Cancer Center at Orlando
state: Florida
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Prairie Village
country: United States
facility: CCOP - Kansas City
state: Kansas
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Alexandria
country: United States
facility: Tulane Cancer Center Office of Clinical Research
state: Louisiana
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders - Scarborough
state: Maine
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: McLaren Cancer Institute
state: Michigan
city: Grand Rapids
country: United States
facility: Butterworth Hospital at Spectrum Health
state: Michigan
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: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Louis
country: United States
facility: Saint Louis University Cancer Center
state: Missouri
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Mount Laurel
country: United States
facility: Cooper CyberKnife Center
state: New Jersey
city: Sparta
country: United States
facility: Frederick R. and Betty M. Smith Cancer Treatment Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: St. Luke's - Roosevelt Hospital Center - St.Luke's Division
state: New York
city: New York
country: United States
facility: Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Sylvania
country: United States
facility: Flower Hospital Cancer Center
state: Ohio
city: Abington
country: United States
facility: Rosenfeld Cancer Center at Abington Memorial Hospital
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: Philadelphia
country: United States
facility: Frankford Hospital Cancer Center - Torresdale Campus
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Wynnewood
country: United States
facility: Lankenau Cancer Center at Lankenau Hospital
state: Pennsylvania
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Norfolk
country: United States
facility: Sentara Cancer Institute at Sentara Norfolk General Hospital
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
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: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Andrea Bezjak, MD, MSC, FRCPC
role: PRINCIPAL_INVESTIGATOR
affiliation: Mallinckrodt Institute of Radiology at Washington University Medical Center
name: Jeffrey Bradley, MD
role: STUDY_CHAIR
affiliation: University of Colorado, Denver
name: Laurie E. Gaspar, MD, MBA
role: STUDY_CHAIR
affiliation: University of Texas
name: Robert D. Timmerman, MD
role: STUDY_CHAIR
affiliation: Medical College of Wisconsin
name: Elizabeth Gore, MD
role: STUDY_CHAIR
affiliation: Georgia Regents University Cancer Center
name: Feng-Ming Phoenix Konb, MD, PhD
role: STUDY_CHAIR
References:
citation: Bezjak A, Paulus R, Gaspar LE, Timmerman RD, Straube WL, Ryan WF, Garces YI, Pu AT, Singh AK, Videtic GM, McGarry RC, Iyengar P, Pantarotto JR, Urbanic JJ, Sun AY, Daly ME, Grills IS, Sperduto P, Normolle DP, Bradley JD, Choy H. Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non-Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial. J Clin Oncol. 2019 May 20;37(15):1316-1325. doi: 10.1200/JCO.18.00622. Epub 2019 Apr 3.
citation: Levy A, Guckenberger M, Hurkmans C, Nestle U, Belderbos J, De Ruysscher D, Faivre-Finn C, Le Pechoux C. SBRT Dose and Survival in Non-Small Cell Lung Cancer: In Regard to Koshy et al. Int J Radiat Oncol Biol Phys. 2015 Jul 15;92(4):945-6. doi: 10.1016/j.ijrobp.2015.03.032. No abstract available.