Chemotherapy Plus Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

Topotecan/Paclitaxel Induction Followed by Consolidation Chemoradiotherapy for Limited Stage Small Cell Lung Cancer: A Phase II Study

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 drug and giving them before and with radiation therapy may be an effective treatment for limited-stage small cell lung cancer.

PURPOSE: Phase II trial to study the effectiveness of chemotherapy plus radiation therapy in treating patients who have limited-stage small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Radiation: radiation therapy; Drug: etoposide; Drug: paclitaxel; Biological: filgrastim; Drug: topotecan hydrochloride

Detailed Description

OBJECTIVES: I. Determine the complete response rate to 2 courses of paclitaxel and topotecan followed by consolidation chemoradiotherapy in patients with limited stage small cell lung cancer. II. Determine the toxic effects of this regimen in this patient population. III. Describe the pattern of relapse, documenting carefully the location of relapse with respect to the original disease volume and the radiation treatment field in these patients. IV. Determine the overall and failure free survival of these patients.

OUTLINE: Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 1. Filgrastim (G-CSF) is administered subcutaneously every day starting on day 6 until blood counts recover. The course is repeated once beginning on day 22. After restaging, patients begin thoracic radiotherapy daily, five days per week, for 6-7 weeks. On the same day that radiotherapy begins, patients receive carboplatin IV over 1 hour (day 43) and etoposide IV over 1 hour daily for 3 days (days 43-45). The consolidation chemotherapy is repeated every 21 days for a total of 3 courses. Patients with stable or responding disease undergo prophylactic cranial irradiation. Patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then at least every year.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within 15-18 months.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Veterans Affairs Medical Center - Birmingham
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
    • San Francisco, California, United States, 94115-0128
      • UCSF Cancer Center and Cancer Research Institute
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • CCOP - Christiana Care Health Services
  • District of Columbia
    • Washington, District of Columbia, United States, 20307-5000
      • Walter Reed Army Medical Center
    • Washington, District of Columbia, United States, 20007
      • Vincent T. Lombardi Cancer Research Center, Georgetown University
  • Florida
    • Miami Beach, Florida, United States, 33140
      • CCOP - Mount Sinai Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Veterans Affairs Medical Center - Chicago (Westside Hospital)
    • Chicago, Illinois, United States, 60637
      • University of Chicago Cancer Research Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago Health Sciences Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Maine
    • Togus, Maine, United States, 04330
      • Veterans Affairs Medical Center - Togus
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene & Stewart Greenebaum Cancer Center, University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana-Farber Cancer Institute
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Memorial Medical Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Veterans Affairs Medical Center - Columbia (Truman Memorial)
    • Columbia, Missouri, United States, 65203
      • Ellis Fischel Cancer Center - Columbia
    • Saint Louis, Missouri, United States, 63110
      • Barnes-Jewish Hospital
    • Saint Louis, Missouri, United States, 63131
      • Missouri Baptist Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68198-3330
      • University of Nebraska Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • CCOP - Southern Nevada Cancer Research Foundation
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Norris Cotton Cancer Center
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute
    • Buffalo, New York, United States, 14215
      • Veterans Affairs Medical Center - Buffalo
    • Manhasset, New York, United States, 11030
      • CCOP - North Shore University Hospital
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital
    • New York, New York, United States, 10021
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10021
      • New York Presbyterian Hospital - Cornell Campus
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center, NY
    • Syracuse, New York, United States, 13210
      • State University of New York - Upstate Medical University
    • Syracuse, New York, United States, 13210
      • Veterans Affairs Medical Center - Syracuse
    • Syracuse, New York, United States, 13210
      • CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7295
      • Lineberger Comprehensive Cancer Center, UNC
    • Durham, North Carolina, United States, 27705
      • Veterans Affairs Medical Center - Durham
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center
    • Winston-Salem, North Carolina, United States, 27104-4241
      • CCOP - Southeast Cancer Control Consortium
    • Winston-Salem, North Carolina, United States, 27157-1082
      • Comprehensive Cancer Center of Wake Forest University Baptist Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Arthur G. James Cancer Hospital - Ohio State University
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425-0721
      • Medical University of South Carolina
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee, Memphis Cancer Center
  • Vermont
    • Burlington, Vermont, United States, 05401-3498
      • Vermont Cancer Center
    • White River Junction, Vermont, United States, 05009
      • Veterans Affairs Medical Center - White River Junction
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • MBCCOP - Massey Cancer Center
    • Richmond, Virginia, United States, 23249
      • Veterans Affairs Medical Center - Richmond

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 limited stage small cell lung cancer Includes disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal lymph nodes Clinically suspected or confirmed supraclavicular lymph node metastases and pleural effusions that are visible on plain chest radiographs, whether cytologically positive or not, are not eligible Unidimensionally or bidimensionally measurable disease

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL SGOT less than 2 times upper limit of normal (ULN) Renal: Creatinine no greater than ULN Other: Not pregnant or nursing Fertile patients must use effective contraception No concurrent active second malignancy except nonmelanoma skin cancer (i.e., completed therapy and considered to be at less than 30% risk of relapse)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for small cell lung cancer No other concurrent chemotherapy Endocrine therapy: No concurrent steroids except for adrenal failure No concurrent hormones except for nondisease related conditions (e.g., insulin for diabetes) No concurrent dexamethasone except for intermittent use as an antiemetic or as an adjunct to prophylactic cranial irradiation Radiotherapy: No prior mediastinal radiotherapy Surgery: Not specified

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: chemotherapy + radiation therapy; Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 1. Filgrastim (G-CSF) is administered subcutaneously every day starting on day 6 until blood counts recover. The course is repeated once beginning on day 22. After restaging, patients begin thoracic radiotherapy daily, five days per week, for 6-7 weeks. On the same day that radiotherapy begins, patients receive carboplatin IV over 1 hour (day 43) and etoposide IV over 1 hour daily for 3 days (days 43-45). The consolidation chemotherapy is repeated every 21 days for a total of 3 courses. Patients with stable or responding disease undergo prophylactic cranial irradiation. Patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then at least every year.

Drug: carboplatin; Radiation: radiation therapy; Drug: etoposide; Drug: paclitaxel; Biological: filgrastim; Drug: topotecan hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
response rate	Up to 5 years
overall survival	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Alan P. Lyss, MD, Missouri Baptist Cancer Center

Publications and helpful links

General Publications

• Bogart JA, Herndon JE 2nd, Lyss AP, Watson D, Miller AA, Lee ME, Turrisi AT, Green MR; Cancer and Leukemia Group B study 39808. 70 Gy thoracic radiotherapy is feasible concurrent with chemotherapy for limited-stage small-cell lung cancer: analysis of Cancer and Leukemia Group B study 39808. Int J Radiat Oncol Biol Phys. 2004 Jun 1;59(2):460-8. doi: 10.1016/j.ijrobp.2003.10.021.
• Cicchetti MG, Bogart J, Lyss A, et al.: Spinal cord dose in limited stage small cell lung cancer: a preliminary Quality Assurance Review Committee (QARC) report on CALGB 39808, using target thoracic radiotherapy (TRT) doses of 60 - 70 Gy. [Abstract] Int J Radiat Oncol Biol Phys 51(3 suppl 1): A-656, 356, 2001.
• Lyss AP, Herndon JE, Bogart JE, et al.: Topotecan (Topo) + paclitaxel (Tax) + G-CSF (G) induction followed by concurrent chemoradiotherapy (CCRT) for patients (pts) with limited stage small cell lung cancer (L-SCLC): preliminary analysis of CALGB 39808. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1270, 2001.

Study record dates

Study Major Dates

• Study Start: March 1, 1999
• Primary Completion (Actual): June 1, 2004
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: July 21, 2004
• First Posted (Estimate): July 22, 2004

Study Record Updates

• Last Update Posted (Estimate): July 20, 2016
• Last Update Submitted That Met QC Criteria: July 19, 2016
• Last Verified: July 1, 2016

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; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Etoposide; Paclitaxel; Topotecan
• Other Study ID Numbers: CALGB-39808; U10CA031946 (U.S. NIH Grant/Contract); CLB-39808; CDR0000066958 (Registry Identifier: NCI Physician Data Query)