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

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)

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.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Radiation: Prophylactic Cranial Irradiation; Radiation: Radiation Therapy

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 97
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
    • Sudbury, Ontario, Canada, P3E 5J1
      • Northeastern Ontario Regional Cancer Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
• Israel
  • Petach Tikva, Israel, 49100
    • Rabin Medical Center - Beilinson Campus
  • Tel Aviv, Israel, 64239
    • Tel-Aviv Sourasky Medical Center
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
      • Arizona Oncology - Tucson
  • California
    • Fresno, California, United States, 93720
      • Saint Agnes Cancer Center at Saint Agnes Medical Center
    • Sacramento, California, United States, 95815
      • Radiological Associates of Sacramento Medical Group, Incorporated
  • Colorado
    • Colorado Springs, Colorado, United States, 80933
      • Penrose Cancer Center at Penrose Hospital
    • Fort Collins, Colorado, United States, 80528
      • Poudre Valley Radiation Oncology
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
    • New Britain, Connecticut, United States, 06050
      • George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus
  • Florida
    • Gainesville, Florida, United States, 32610-0232
      • University of Florida Shands Cancer Center
    • Jacksonville, Florida, United States, 32207
      • Baptist Cancer Institute - Jacksonville
    • Jacksonville, Florida, United States, 32207
      • Integrated Community Oncology Network at Southside Cancer Center
    • Jacksonville, Florida, United States, 32258
      • Baptist Medical Center South
    • Jacksonville Beach, Florida, United States, 32250
      • Integrated Community Oncology Network
    • Orange Park, Florida, United States, 32073
      • Integrated Community Oncology Network - Orange Park
    • Orlando, Florida, United States, 32803-1273
      • Florida Hospital Cancer Institute at Florida Hospital Orlando
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center at Orlando
    • Palatka, Florida, United States, 32177
      • Florida Cancer Center - Palatka
    • Saint Augustine, Florida, United States, 32086
      • Flagler Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
    • Atlanta, Georgia, United States, 30308
      • Emory Crawford Long Hospital
    • Atlanta, Georgia, United States, 30303
      • Georgia Cancer Center for Excellence at Grady Memorial Hospital
  • Illinois
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Springfield, Illinois, United States, 62702
      • Cancer Institute at St. John's Hospital
  • Indiana
    • Anderson, Indiana, United States, 46016
      • Saint John's Cancer Center at Saint John's Medical Center
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Regional Cancer Center at Parkview Health
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates Southwest
    • Goshen, Indiana, United States, 46526
      • Center for Cancer Care at Goshen General Hospital
    • Indianapolis, Indiana, United States, 46219
      • Community Regional Cancer Care at Community Hospital East
    • Indianapolis, Indiana, United States, 46256
      • Community Regional Cancer Care at Community Hospital North
  • Kansas
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Overland Park, Kansas, United States, 66210
      • Kansas City Cancer Centers - Southwest
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
    • Louisville, Kentucky, United States, 40202
      • James Graham Brown Cancer Center at University of Louisville
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Clinton Township, Michigan, United States, 48038
      • Henry Ford Macomb Hospital
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grand Rapids, Michigan, United States, 49503
      • Butterworth Hospital at Spectrum Health
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Health Care
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Cancer Clinic
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Cancer Institute of Cape Girardeau, LLC
    • Kansas City, Missouri, United States, 64154
      • Kansas City Cancer Centers - North
    • Kansas City, Missouri, United States, 64131
      • Kansas City Cancer Centers - South
    • Saint Louis, Missouri, United States, 63141
      • Barnes-Jewish West County Hospital
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Estabrook Cancer Center
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medical Center
  • Nevada
    • Reno, Nevada, United States, 89502
      • Renown Institute for Cancer at Renown Regional Medical Center
  • New Hampshire
    • Manchester, New Hampshire, United States, 03103
      • Elliot Regional Cancer Center at Elliot Hospital
  • New Jersey
    • Sparta, New Jersey, United States, 07871
      • Frederick R. and Betty M. Smith Cancer Treatment Center
    • Voorhees, New Jersey, United States, 08043
      • Cancer Institute of New Jersey at Cooper - Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-5636
      • University of New Mexico Cancer Center
  • New York
    • Albany, New York, United States, 12206
      • New York Oncology Hematology, PC at Albany Regional Cancer Care
    • New York, New York, United States, 10016
      • NYU Cancer Institute at New York University Medical Center
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157-1096
      • Wake Forest University Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Regional Cancer Center at Forsyth Medical Center
  • North Dakota
    • Minot, North Dakota, United States, 58701
      • Trinity Cancercare Center
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Akron, Ohio, United States, 44309-2090
      • Summa Center for Cancer Care at Akron City Hospital
    • Barberton, Ohio, United States, 44203
      • Barberton Citizens Hospital
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106-5065
      • Case Comprehensive Cancer Center
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center at Fairview Hospital
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Cancer Center at Hillcrest Hospital
    • Mentor, Ohio, United States, 44060
      • Lake/University Ireland Cancer Center
    • Middleburg Heights, Ohio, United States, 44130
      • Southwest General Health Center
    • Orange Village, Ohio, United States, 44122
      • UHHS Chagrin Highlands Medical Center
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Parma, Ohio, United States, 44129
      • Parma Community General Hospital
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Toledo, Ohio, United States, 43623
      • St. Anne Mercy Hospital
    • Westlake, Ohio, United States, 44145
      • UHHS Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Natalie Warren Bryant Cancer Center at St. Francis Hospital
  • Oregon
    • Grants Pass, Oregon, United States, 97527
      • Three Rivers Community Hospital
    • Medford, Oregon, United States, 97504
      • Dubs Cancer Center at Rogue Valley Medical Center
  • Pennsylvania
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • Philadelphia, Pennsylvania, United States, 19107-5541
      • Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Texas
    • Arlington, Texas, United States, 76014
      • Texas Oncology, PA at Texas Cancer Center - Arlington South
    • Denton, Texas, United States, 76210
      • Texas Oncology, PA at Texas Cancer Center - Denton South
    • Fort Worth, Texas, United States, 76104
      • Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital
    • Galveston, Texas, United States, 77555-0361
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77024
      • Memorial Hermann Hospital - Memorial City
    • Longview, Texas, United States, 75601
      • Longview Cancer Center
    • San Antonio, Texas, United States, 78217
      • Cancer Care Centers of South Texas - Northeast
    • Sherman, Texas, United States, 75090
      • Texas Oncology, PA at Texas Cancer Center - Sherman
    • Sugar Land, Texas, United States, 77479
      • Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land
    • Tyler, Texas, United States, 75702
      • Tyler Cancer Center
    • Wichita Falls, Texas, United States, 76310
      • Texas Oncology, PA - Wichita Falls
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-6164
      • University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee
    • Racine, Wisconsin, United States, 53405
      • All Saints Cancer Center at Wheaton Franciscan Healthcare
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Riverview UW Cancer Center at Riverview Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PCI; Prophylactic Cranial Irradiation (PCI)	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.; Other Names: PCI
Experimental: PCI + Consolidation RT; Prophylactic Cranial Irradiation (PCI) plus consolidative radiation therapy (RT) to locoregional and residual metastatic disease	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.; Other Names: PCI; Radiation: 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; Other Names: RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); NRG Oncology
• Investigators: Principal Investigator: Elizabeth M. Gore, MD, Medical College of Wisconsin; Principal Investigator: Alexander Sun, MD, Princess Margaret Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: January 22, 2010
• First Submitted That Met QC Criteria: January 22, 2010
• First Posted (Estimate): January 25, 2010

Study Record Updates

• Last Update Posted (Actual): December 12, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: extensive stage small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma
• Other Study ID Numbers: RTOG 0937; CDR0000663959; NCI-2011-02008 (Registry Identifier: Clinical Trial Reporting Program (CTRP))