Radiation Therapy in Treating Patients With Extensive Stage Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

Randomized Phase II Study Comparing Prophylactic Cranial Irradiation Alone to Prophylactic Cranial Irradiation and Consolidative Extra-Cranial Irradiation for Extensive Disease Small Cell Lung Cancer (ED-SCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01055197
• Other study ID #: RTOG 0937
• Secondary ID: CDR0000663959NCI
• Status: Completed
• Phase: Phase 2
• Start date: March 2010
• Est. completion date: December 2016

Study information

• Verified date: July 2018
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Radiation therapy uses high energy x-rays to kill tumor cells. This may be an effective treatment for extensive stage small cell lung cancer.

PURPOSE: This randomized phase II trial is comparing how well radiation therapy to the brain works when given with or without radiation therapy to other areas of the body in treating patients with extensive stage small cell lung cancer.

Description:

OBJECTIVES:

Primary

• To compare the 1-year overall median survival rate in patients with extensive stage small cell lung cancer treated with prophylactic cranial irradiation with vs without consolidative extracranial radiotherapy following platinum-based chemotherapy.

Secondary

• To compare treatment-related adverse events in these patients.

• To evaluate patterns of failure in these patients.

• To compare the time to first failure in these patients.

• To evaluate the percentage of the planned radiotherapy dose given to each site.

OUTLINE: This is a multicenter study. Patients are stratified according to response to prior treatment (complete response vs partial response) and number of metastatic lesions (1 vs 2-3). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients undergo prophylactic cranial irradiation 5 days per week for 2 weeks.

• Arm II: Patients undergo prophylactic cranial irradiation as in arm I. Patients also undergo consolidative extracranial radiotherapy to locoregional and residual metastatic disease 5 days per week for 2-3 weeks.

After completion of study treatment, patients are followed up at 2 weeks; at 1, 2, 6, 9, and 12 months; every 6 months for 2 years; and then annually thereafter.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 97
• Est. completion date: December 2016
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed extensive stage small cell lung cancer (SCLC) diagnosed within the past 6 months*

• Has 1-4 extracranial metastatic lesions NOTE: *Diagnosis made before treatment with chemotherapy

• Has completed 4-6 courses of platinum-based chemotherapy within the past 8 weeks AND meets the following criteria:

• Radiographic partial or complete response to chemotherapy in = 1 site of disease according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (if radiotherapy has been delivered to primary disease with chemotherapy, there must be complete or partial response in = 1 of the sites that has not been treated with radiotherapy)

• No progression in any site

• No limited stage SCLC, even if disease progressed

• No brain or central nervous system (CNS) metastases

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Absolute neutrophil count (ANC) = 1,000/mm^3

• Platelets = 75,000/mm^3

• Hemoglobin = 8.0 g/dL (the use of transfusion or other intervention is allowed)

• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 times upper limit of normal (ULN) (for patients who will receive radiotherapy to the liver)

• Serum bilirubin < 1.5 times ULN (for patients who will receive radiotherapy to the liver)

• Serum creatinine < 1.5 times ULN (for patients who will receive radiotherapy to the kidneys)

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No severe, active co-morbidity, defined as any of the following:

• Acute bacterial or fungal infection requiring IV antibiotics at the time of study registration

• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of study registration

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• Recovered from prior chemotherapy (i.e., toxicities = grade 1 [except for neuropathy and alopecia])

• Thoracic radiotherapy administered concurrently with or before chemotherapy for the current diagnosis allowed (these patients will not receive mediastinal radiotherapy per protocol)

• No prior radiotherapy to the region of this cancer that would result in overlap of radiotherapy fields

• No concurrent chemotherapy

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Radiation:
• Prophylactic Cranial Irradiation
Prophylactic Cranial Irradiation (PCI) to the brain in ten once-daily fractions of 2.5 Gy, five days per week, for a total of 25 Gy.
• Radiation Therapy
Radiation Therapy (RT) to locoregional and residual metastatic disease in 15 once daily fractions of 3.0 Gy, 5 days per week, for a total of 45 Gy

Locations

Country	Name	City	State
Canada	London Regional Cancer Program at London Health Sciences Centre	London	Ontario
Canada	Allan Blair Cancer Centre at Pasqua Hospital	Regina	Saskatchewan
Canada	Northeastern Ontario Regional Cancer Centre	Sudbury	Ontario
Canada	Princess Margaret Hospital	Toronto	Ontario
Canada	British Columbia Cancer Agency - Vancouver Cancer Centre	Vancouver	British Columbia
Israel	Rabin Medical Center - Beilinson Campus	Petach Tikva
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
United States	Hickman Cancer Center at Bixby Medical Center	Adrian	Michigan
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	New York Oncology Hematology, PC at Albany Regional Cancer Care	Albany	New York
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Saint John's Cancer Center at Saint John's Medical Center	Anderson	Indiana
United States	Texas Oncology, PA at Texas Cancer Center - Arlington South	Arlington	Texas
United States	Emory Crawford Long Hospital	Atlanta	Georgia
United States	Georgia Cancer Center for Excellence at Grady Memorial Hospital	Atlanta	Georgia
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Henry Ford Macomb Hospital	Clinton Township	Michigan
United States	Penrose Cancer Center at Penrose Hospital	Colorado Springs	Colorado
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Texas Oncology, PA at Texas Cancer Center - Denton South	Denton	Texas
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Northeast Radiation Oncology Center	Dunmore	Pennsylvania
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Poudre Valley Radiation Oncology	Fort Collins	Colorado
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	Radiation Oncology Associates Southwest	Fort Wayne	Indiana
United States	Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital	Fort Worth	Texas
United States	Saint Agnes Cancer Center at Saint Agnes Medical Center	Fresno	California
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	University of Texas Medical Branch	Galveston	Texas
United States	Center for Cancer Care at Goshen General Hospital	Goshen	Indiana
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Three Rivers Community Hospital	Grants Pass	Oregon
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Memorial Hermann Hospital - Memorial City	Houston	Texas
United States	Community Regional Cancer Care at Community Hospital East	Indianapolis	Indiana
United States	Community Regional Cancer Care at Community Hospital North	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida
United States	Baptist Medical Center South	Jacksonville	Florida
United States	Integrated Community Oncology Network at Southside Cancer Center	Jacksonville	Florida
United States	Integrated Community Oncology Network	Jacksonville Beach	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kansas City Cancer Centers - North	Kansas City	Missouri
United States	Kansas City Cancer Centers - South	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Longview Cancer Center	Longview	Texas
United States	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	University of Wisconsin Paul P. Carbone Comprehensive Cancer Center	Madison	Wisconsin
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Hillcrest Cancer Center at Hillcrest Hospital	Mayfield Heights	Ohio
United States	Dubs Cancer Center at Rogue Valley Medical Center	Medford	Oregon
United States	Lake/University Ireland Cancer Center	Mentor	Ohio
United States	Southwest General Health Center	Middleburg Heights	Ohio
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Trinity CancerCare Center	Minot	North Dakota
United States	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
United States	Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center	New York	New York
United States	NYU Cancer Institute at New York University Medical Center	New York	New York
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	Nebraska Medical Center	Omaha	Nebraska
United States	Integrated Community Oncology Network - Orange Park	Orange Park	Florida
United States	UHHS Chagrin Highlands Medical Center	Orange Village	Ohio
United States	St. Charles Mercy Hospital	Oregon	Ohio
United States	Florida Hospital Cancer Institute at Florida Hospital Orlando	Orlando	Florida
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Kansas City Cancer Centers - Southwest	Overland Park	Kansas
United States	Florida Cancer Center - Palatka	Palatka	Florida
United States	Parma Community General Hospital	Parma	Ohio
United States	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	All Saints Cancer Center at Wheaton Franciscan Healthcare	Racine	Wisconsin
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Renown Institute for Cancer at Renown Regional Medical Center	Reno	Nevada
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Flagler Cancer Center	Saint Augustine	Florida
United States	Barnes-Jewish West County Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Cancer Care Centers of South Texas - Northeast	San Antonio	Texas
United States	North Coast Cancer Care, Incorporated	Sandusky	Ohio
United States	Texas Oncology, PA at Texas Cancer Center - Sherman	Sherman	Texas
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	Flower Hospital Cancer Center	Sylvania	Ohio
United States	St. Anne Mercy Hospital	Toledo	Ohio
United States	Arizona Oncology - Tucson	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Tyler Cancer Center	Tyler	Texas
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	St. John Macomb Hospital	Warren	Michigan
United States	UHHS Westlake Medical Center	Westlake	Ohio
United States	Texas Oncology, PA - Wichita Falls	Wichita Falls	Texas
United States	Forsyth Regional Cancer Center at Forsyth Medical Center	Winston-Salem	North Carolina
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina
United States	Riverview UW Cancer Center at Riverview Hospital	Wisconsin Rapids	Wisconsin
United States	Cleveland Clinic - Wooster	Wooster	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada,  Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (12-month Rate Reported)	Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur when all patients had been potentially followed for at least 12 months. The 12-month rate is reported.	From randomization to last follow-up. Analysis occurred after all patients had been potentially followed for at least 12 months. Maximum follow-up at time of analysis was 46.0 months.
Secondary	Percentage of Patients Experiencing a Grade 3 or Higher Adverse Event	Adverse events (AE) are graded using CTCAE v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE.	From randomization to last follow-up. Analysis occurred after all patients had been potentially followed for at least 12 months. Maximum follow-up at time of analysis was 46.0 months.
Secondary	Patterns of Failure - Number of Patients With Failure by Site	Failure was defined as progressive disease in areas treated with radiation development of measurable disease at sites that had achieved a complete response either with chemotherapy prior to study entry or following radiation, or development of new disease characteristic of small-cell lung cancer dissemination as determined by imaging [per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1] and physical examination. A patient could be counted in more than one category.	From randomization to last follow-up. Analysis occurred after all patients had been potentially followed for at least 12 months. Maximum follow-up at time of analysis was 46.0 months.
Secondary	First Failure (12-month Rate Reported)	Failure was defined as progressive disease in areas treated with radiation development of measurable disease at sites that had achieved a complete response either with chemotherapy prior to study entry or following radiation, or development of new disease characteristic of small-cell lung cancer dissemination as determined by imaging [per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1] and physical examination. Time to first failure is defined as time from randomization to the date of first failure, last known follow-up (censored), or death (competing risk). First failure rates are estimated using the cumulative incidence method.	From randomization to last follow-up. Analysis occurred after all patients had been potentially followed for at least 12 months. Maximum follow-up at time of analysis was 46.0 months.
Secondary	Percentage of Planned Radiotherapy Dose (All Sites) That Was Delivered	Total dose to the brain was to be 25 Gy for all patients. For patients on PCI+consolidative RT, patients were to get 45 Gy at 3 Gy per fraction to the locoregional area as well as to residual metastatic disease. Alternatively, these regions could have received 30-40 Gy in 10 fractions. The total planned dose was determined, and a percentage was calculated based for each patient as total delivered dose / total planned dose.	From start to end of radiation therapy; up to 32 days for Prophylactic Cranial Irradiation arm, up to 68 days for Prophylactic Cranial Irradiation + Consolidation Radiotherapy arm.