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

Paclitaxel/Topotecan/Etoposide (EtopoTax) 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 chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy and 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:

• Determine the complete and overall response rates in patients with limited stage small cell lung cancer treated with induction chemotherapy comprising paclitaxel, topotecan, and etoposide followed by consolidation chemoradiotherapy.
• Determine the toxicity of this regimen in these patients.
• Determine the overall and failure-free survival of patients treated with this regimen.
• Determine the overall (partial and complete) response rate in patients treated with this induction chemotherapy regimen.

OUTLINE: This is a multicenter study.

• Induction therapy: Patients receive paclitaxel IV over 3 hours on days 1 and 22, oral topotecan on days 2-4 and 23-25, and oral etoposide on days 5-7 and 26-28. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on days 8 and 29 and continuing until blood counts recover.
• Consolidation therapy: Patients receive carboplatin IV over 1 hour on days 43, 64, and 85 and etoposide IV over 1 hour on days 43-45, 64-66, and 85-87. Patients undergo radiotherapy daily 5 days per week beginning on day 43 and continuing for 6-7 weeks.

Patients with rapid disease progression discontinue study therapy.

Patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 25-60 patients will be accrued for this study within 10 months.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233-1996
      • Veterans Affairs Medical Center - Birmingham
  • California
    • La Jolla, California, United States, 92093-0658
      • University of California San Diego Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center - San Francisco
    • San Francisco, California, United States, 94143-0128
      • 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
      • Lombardi Cancer Center
  • 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, 60637-1470
      • University of Chicago Cancer Research Center
  • Indiana
    • South Bend, Indiana, United States, 46601
      • CCOP - Northern Indiana CR Consortium
  • Iowa
    • Iowa City, Iowa, United States, 52242-1009
      • Holden Comprehensive Cancer Center
  • Maine
    • Togus, Maine, United States, 04330
      • Veterans Affairs Medical Center - Togus
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Marlene and 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 - University Campus
  • Minnesota
    • Minneapolis, Minnesota, United States, 55417
      • Veterans Affairs Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center
  • 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, 68198-7680
      • 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, 03756-0002
      • 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, 13217
      • 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 at Wake Forest University
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Arthur G. James Cancer Hospital - Ohio State University
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Western Pennsylvania Hospital
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38104
      • Veterans Affairs Medical Center - Memphis
    • Memphis, Tennessee, United States, 38103
      • University of Tennessee Cancer Institute
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Green Mountain Oncology Group
    • 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 to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

  • Limited stage defined as disease restricted to one hemithorax with regional lymph node metastases including hilar, ipsilateral, and contralateral mediastinal lymph nodes

• Measurable disease

  • At least 20 mm by conventional techniques OR
  • At least 10 mm by spiral CT scan

  • Lesions not considered measurable include the following:

    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
    • Tumor lesions in a previously irradiated area
• No clinically suspected or confirmed supraclavicular lymph node metastases
• No pleural effusions visible on plain chest radiographs, regardless of cytology

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 100,00/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
• Creatinine clearance no greater than 150 mL/min for men or 130 mL/min for women

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other currently active malignancy except non-melanoma skin cancer
• Patients must have completed therapy for any other malignancy and be considered to be at less than 30% risk of relapse

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• No concurrent filgrastim (G-CSF) during consolidation therapy

Chemotherapy:

• No prior chemotherapy for small cell lung cancer
• No other concurrent chemotherapy

Endocrine therapy:

• No concurrent hormonal therapy except:

  • Steroids for adrenal failure
  • Hormones for non-disease-related conditions (e.g., insulin for diabetes)
  • Intermittent use of dexamethasone as an antiemetic or as an adjunct to prophylactic cranial irradiation

Radiotherapy:

• See Disease Characteristics
• No prior chest 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; Induction therapy: Patients receive paclitaxel IV over 3 hours on days 1 and 22, oral topotecan on days 2-4 and 23-25, and oral etoposide on days 5-7 and 26-28. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on days 8 and 29 and continuing until blood counts recover. Consolidation therapy: Patients receive carboplatin IV over 1 hour on days 43, 64, and 85 and etoposide IV over 1 hour on days 43-45, 64-66, and 85-87. Patients undergo radiotherapy daily 5 days per week beginning on day 43 and continuing for 6-7 weeks. Patients with rapid disease progression discontinue study therapy. Patients are followed at least every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

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
overall response rate	up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	up to 5 years
failure-free survival	up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Antonius A. Miller, MD, Wake Forest University Health Sciences

Publications and helpful links

General Publications

• Miller AA, Wang XF, Bogart JA, Hodgson LD, Rocha Lima CM, Radford JE, Vokes EE, Green MR; Cancer and Leukemia Group B (CALGB). Phase II trial of paclitaxel-topotecan-etoposide followed by consolidation chemoradiotherapy for limited-stage small cell lung cancer: CALGB 30002. J Thorac Oncol. 2007 Jul;2(7):645-51. doi: 10.1097/JTO.0b013e318074bbf5.

Study record dates

Study Major Dates

• Study Start: September 1, 2001
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: April 9, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 19, 2016
• Last Update Submitted That Met QC Criteria: July 15, 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-30002; U10CA031946 (U.S. NIH Grant/Contract); CLB-30002; CDR0000069313 (Registry Identifier: NCI Physician Data Query)