Cisplatin, Etoposide, and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

A Phase II Study Of Accelerated High Dose Thoracic Irradiation With Concurrent Chemotherapy For Patients With Limited Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving cisplatin and etoposide together with radiation therapy works in treating patients with limited-stage small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Cisplatin; Drug: Etoposide; Radiation: Radiation therapy

Detailed Description

OBJECTIVES:

• Determine the response rate of patients with limited stage small cell lung cancer treated with cisplatin and etoposide combined with accelerated high-dose thoracic radiotherapy.
• Determine the progression-free and overall survival in patients treated with this regimen.
• Determine the qualitative and quantitative toxicity and reversibility of toxicity of this regimen in these patients.

OUTLINE: Patients undergo radiotherapy once daily 5 days a week for approximately 3 weeks and then twice daily 5 days a week for approximately 2 weeks (a total of 9 treatment days during the final 2-week treatment period). Beginning on the first day of radiotherapy, patients receive cisplatin IV over 2 hours and etoposide IV over 1 hour on day 1 and oral etoposide once daily on days 2 and 3. Chemotherapy repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 71 patients will be accrued for this study within 18 months.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Comprehensive Cancer Center at University of Alabama at Birmingham
  • California
    • Castro Valley, California, United States, 94546
      • Eden Medical Center
    • Hayward, California, United States, 94545
      • Saint Rose Hospital
    • Oakland, California, United States, 94609
      • Alta Bates Summit Medical Center - Summit Campus
    • Oakland, California, United States, 94609
      • CCOP - Bay Area Tumor Institute
    • Oakland, California, United States, 94602
      • Highland General Hospital at St. George's University School of Medicine
    • Pleasanton, California, United States, 94588
      • Valley Care Medical Center
    • Pomona, California, United States, 91767
      • Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
    • San Pablo, California, United States, 94806
      • J.C. Robinson, M.D. Regional Cancer Center
  • Georgia
    • Savannah, Georgia, United States, 31403-3089
      • Curtis & Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois, PC - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology Hematology Associates of Central Illinois, PC - Peoria
    • Peoria, Illinois, United States, 61615-7827
      • OSF St. Francis Medical Center
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • St. Margaret's Hospital
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Elkhart, Indiana, United States, 46515
      • Elkhart General Hospital
    • Kokomo, Indiana, United States, 46904
      • Howard Community Hospital at Howard Regional Health System
    • La Porte, Indiana, United States, 46350
      • Center for Cancer Therapy at LaPorte Hospital and Health Services
    • South Bend, Indiana, United States, 46601
      • Memorial Hospital of South Bend
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
    • South Bend, Indiana, United States, 46617
      • Saint Joseph Regional Medical Center
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center at Finley Hospital
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Cancer Treatment Center at the Medical Center - Bowling Green
    • Lexington, Kentucky, United States, 40536-0293
      • Markey Cancer Center at University of Kentucky Chandler Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Ann Arbor, Michigan, United States, 48106-0995
      • St. Joseph Mercy Cancer Center at St. Joseph Mercy Hospital
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48202
      • Josephine Ford Cancer Center at Henry Ford Hospital
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Hospital
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
    • Lansing, Michigan, United States, 48909
      • Sparrow Regional Cancer Center
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute - Saginaw
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
    • Saint Louis, Missouri, United States, 63110
      • Siteman Cancer Center at Barnes-Jewish Hospital
  • New Jersey
    • Toms River, New Jersey, United States, 08755
      • J. Phillip Citta Regional Cancer Center at Community Medical Center
    • Trenton, New Jersey, United States, 08629
      • Fox Chase Cancer Center at St. Francis Medical Center
    • Vineland, New Jersey, United States, 08360
      • South Jersey Healthcare Regional Cancer Center
  • New York
    • Plattsburgh, New York, United States, 12901
      • Fitzpatrick Cancer Center at Champlain Valley Physicians Hospital Medical Center
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Radiation Oncology
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Wilson, North Carolina, United States, 27893
      • Wilmed Radiation Oncology Services
  • Ohio
    • Akron, Ohio, United States, 44309-2090
      • Akron City Hospital
    • Canton, Ohio, United States, 44710-1799
      • Aultman Hospital Cancer Center at Aultman Health Foundation
    • 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, 44112
      • Huron Hospital Cancer Care Center
    • Cleveland, Ohio, United States, 44119
      • Euclid Hospital
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Cancer Center at Hillcrest Hospital
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Warrensville Heights, Ohio, United States, 44122
      • South Pointe Hospital Cancer Care Center
    • Wooster, Ohio, United States, 44691
      • Cancer Treatment Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Pennsylvania
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Bryn Mawr Hospital
    • Paoli, Pennsylvania, United States, 19301-1792
      • Paoli Memorial Hospital
    • Reading, Pennsylvania, United States, 19612-6052
      • Reading Hospital and Medical Center
    • Wynnewood, Pennsylvania, United States, 19096
      • CCOP - MainLine Health
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Cancer Center at Lankenau Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Rapid City Regional Hospital
  • Texas
    • Houston, Texas, United States, 77030-4009
      • M.D. Anderson Cancer Center at University of Texas
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center - East Campus
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
    • Salt Lake City, Utah, United States, 84106
      • Utah Cancer Specialists at UCS Cancer Center
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Schiffler Cancer Center at Wheeling Hospital
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee
    • Milwaukee, Wisconsin, United States, 53211
      • Columbia St. Mary's Cancer Care Center

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 small cell carcinoma of the lung by fine needle aspiration biopsy or two positive sputa

• Must have limited disease

  • Stage I, II, IIIA, or IIIB

    • Confined to 1 hemithorax, but excluding the following:

      • T4 tumor based on malignant pleural effusion
      • N3 disease based on contralateral hilar or contralateral supraclavicular involvement
• No pericardial or pleural effusions on chest x-ray (regardless of cytology)
• Measurable or evaluable disease
• Tumor must be able to be encompassed by limited radiotherapy fields without significantly compromising pulmonary function
• No prior complete tumor resection

PATIENT CHARACTERISTICS:

Age

• 18 to 100

Performance status

• Zubrod 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute granulocyte count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3

Hepatic

• Bilirubin no greater than 1.5 mg/dL

Renal

• Creatinine no greater than 1.5 mg/dL

Cardiovascular

• No myocardial infarction within the past 6 months
• No symptomatic heart disease

Pulmonary

• No chronic obstructive pulmonary disease with Forced Expiratory Volume (FEV)-1 no greater than 0.8 liter
• No uncontrolled bronchospasm in the unaffected lung

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Available for follow-up
• No other malignancy within the past 2 years except curatively treated basal cell or squamous cell skin cancer or non-invasive in situ malignancies
• No other concurrent serious medical illness
• No uncontrolled psychiatric illness
• No chronic alcohol or drug abuse

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No prior chemotherapy

Endocrine therapy

• Not specified

Radiotherapy

• No prior radiotherapy to the chest or other area containing a large amount of bone marrow (e.g., more than 75% of pelvic bone)

Surgery

• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Radiation Therapy + Chemotherapy; Accelerated high dose thoracic radiation therapy (RT) with concurrent cisplatin/etoposide chemotherapy, followed by 2 cycles of adjuvant cisplatin/etoposide chemotherapy

Drug: Cisplatin; 60 mg/m2 given intravenously. During RT, give on day 1 and day 22. After completion of RT, on days 43 and 64.; Drug: Etoposide; 120 mg/m2 given intravenously. During RT, give on days 1-3, then days 22-24. After completion of RT, on days 43-45 and days 64-66.; Radiation: Radiation therapy; Large field 28.8 Gy: 1.8 Gy per fraction, 5 days per week for 16 fractions. On days 23-26, BID: use anteroposterior and posteroanterior (AP/PA) fields in a.m. at 1.8 Gy per fraction; boost with 2nd treatment in p.m. at 1.8 Gy per fraction. Then off-cord boost, 1.8 Gy, BID, x last 5 days for a total dose of 61.2 Gy in 5 wks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival at 2 Years	Survival time is defined as time from study registration to the date of death from any cause and survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact.	From registration to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) and Progression-free Survival (PFS) at 1 Year	An event for overall survival is death due to any cause. Overall survival time is defined as time from study registration to the date of death from any cause. An event for progression-free survival is the first of the following: local progression, regional progression, distant metastases, or death due to any cause. Progression-free survival time is defined as time from study registration to the date of first failure. For both outcome measures, patients last known to be alive without failure are censored at the date of last contact. Survival rates are estimated by the Kaplan-Meier method.	From registration to one year.
Median Overall Survival Time and Progression-free Survival Time	An event for overall survival is death due to any cause. Overall survival time is defined as time from study registration to the date of death from any cause. An event for progression-free survival is the first of the following: local progression, regional progression, distant metastases, or death due to any cause. Progression-free survival time is defined as time from study registration to the date of first failure. For both outcome measures, patients last known to be alive without failure are censored at the date of last contact. Survival rates are estimated by the Kaplan-Meier method.	From registration to 2 years
Number of Patients With Acute Treatment-related Grade 3 or 4 Esophagitis	Highest grade treatment-related toxicity per subject was counted. Toxicities were graded using Common Toxicity Criteria (CTC) v 2.0. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening or disabling, Grade 5= Death related to toxicity.	From start of radiation therapy until 90 days following the start of radiation therapy
Frequency of Treatment-related Fatalities at 2 Years	A treatment-related fatality was any death judged to be related to protocol treatment.	From the start of treatment to 2 years
Tumor Response	Response will be recorded as the best response observed two months after the completion of chemoradiation therapy. Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions as measured by MRI, CT, or physical examination (this is the order of preference for measurement). Partial Response (PR): >= 30% decrease in the sum of the longest diameter (LD) of target lesions (order of preference for measurement is MRI, CT, physical examination). Progressive Disease (PD): >= 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions (order of preference for measurement is MRI, CT, physical examination). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.	From the start of treatment to 2 months following the completion of chemotherapy

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Komaki R, Paulus R, Ettinger DS, Videtic GM, Bradley JD, Glisson BS, Langer CJ, Sause WT, Curran WJ Jr, Choy H. Phase II study of accelerated high-dose radiotherapy with concurrent chemotherapy for patients with limited small-cell lung cancer: Radiation Therapy Oncology Group protocol 0239. Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):e531-6. doi: 10.1016/j.ijrobp.2012.01.075. Epub 2012 May 5.
• Komaki R, Moughan J, Ettinger D, et al.: Toxicities in a phase II study of accelerated high dose thoracic radiation therapy (TRT) with concurrent chemotherapy for limited small cell lung cancer (LSCLC) (RTOG 0239). [Abstract] J Clin Oncol 25 (Suppl 18): A-7717, 438s, 2007.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (Actual): May 1, 2012
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: August 6, 2003
• First Submitted That Met QC Criteria: August 6, 2003
• First Posted (Estimate): August 7, 2003

Study Record Updates

• Last Update Posted (Actual): December 22, 2017
• Last Update Submitted That Met QC Criteria: November 27, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: limited 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide; Cisplatin
• Other Study ID Numbers: RTOG-0239; CDR0000271939