Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer

Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF (Filgrastim) Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without filgrastim in treating patients who have extensive-stage small cell lung cancer that has not been previously treated.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Biological: filgrastim; Drug: topotecan hydrochloride; Radiation: WBRT

Detailed Description

OBJECTIVES:

• Determine the tolerability of topotecan and carboplatin with or without filgrastim (G-CSF) in patients with extensive stage small cell lung cancer.
• Determine response and survival rates in patients treated with these regimens.

OUTLINE: This is a multicenter study. The first 12 patients are assigned to 1 of 2 treatment regimens (6 per regimen). The next 33 patients receive treatment based on the toxicity experienced by the first 12.

Regimen A:

• Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and continuing for up to 10 days or until blood counts recover.
• Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, or no more than 1 patient experiences an absolute neutrophil count of less than 500/mm3 for more than 5 days, the next 6 patients begin treatment on regimen B. Otherwise, all patients receive treatment as in regimen A.

Regimen B:

• Patients receive topotecan and carboplatin as in regimen A.
• Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive treatment as in regimen B; otherwise, patients receive treatment as in regimen A.

Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes.

Quality of life is assessed at baseline and at the beginning of each course of chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study within 13.5 months.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5404
      • CCOP - Scottsdale Oncology Program
  • District of Columbia
    • Washington, District of Columbia, United States, 20060
      • MBCCOP-Howard University Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Illinois
    • Peoria, Illinois, United States, 61602
      • CCOP - Illinois Oncology Research Association
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403-1206
      • CCOP - Cedar Rapids Oncology Project
    • Des Moines, Iowa, United States, 50309-1016
      • CCOP - Iowa Oncology Research Association
    • Sioux City, Iowa, United States, 51101-1733
      • Siouxland Hematology-Oncology
  • Kansas
    • Wichita, Kansas, United States, 67214-3882
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214-3882
      • Wichita Community Clinical Oncology Program
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • CCOP - Ochsner
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Ann Arbor Regional
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • CCOP - Duluth
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • CentraCare Health Plaza
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Health System
    • Fargo, North Dakota, United States, 58122
      • CCOP - Merit Care Hospital
    • Grand Forks, North Dakota, United States, 58201
      • Altru Health Systems
  • Ohio
    • Toledo, Ohio, United States, 43623-3456
      • CCOP - Toledo Community Hospital Oncology Program
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212-4772
      • Allegheny General Hospital
  • South Dakota
    • Rapid City, South Dakota, United States, 57709
      • Rapid City Regional 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

  • Previously untreated with chemotherapy
  • No mixed histology

• Metastatic disease outside the chest

  • Contralateral supraclavicular or hilar nodes that cannot be included in a single radiation port OR
  • Cytologically proven malignant pleural effusion
• Measurable disease

• No untreated CNS metastases

  • CNS metastases treated with whole-brain radiotherapy (WBRT) allowed after completion of WBRT

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• AST no greater than 5 times upper limit of normal (ULN)
• Alkaline phosphatase no greater than 5 times ULN
• Bilirubin no greater than 1.5 times ULN OR
• Direct bilirubin no greater than ULN

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• No uncontrolled angina pectoris
• No congestive heart failure within the past 3 months unless ejection fraction is greater than 40%
• No uncontrolled cardiac arrhythmias
• No myocardial infarction within the past 3 months

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant infection
• No hypersensitivity to E. coli-derived proteins
• No other malignancy within the past 3 years except non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• See Disease Characteristics
• At least 5 years since prior chemotherapy for another malignancy
• No prior nitrosoureas

Endocrine therapy:

• Not specified

Radiotherapy:

• See Disease Characteristics
• No prior thoracic radiotherapy
• At least 1 day since prior palliative radiotherapy (except to chest)
• No more than 3 fractions to chest for superior vena cava syndrome allowed
• No concurrent radiotherapy (including thoracic radiotherapy)

Surgery:

• More than 3 weeks since prior major surgery

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Regimen A; Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and continuing for up to 10 days or until blood counts recover. Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes. Quality of life is assessed at baseline and at the beginning of each course of chemotherapy. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.	Drug: carboplatin; Biological: filgrastim; Drug: topotecan hydrochloride; Radiation: WBRT
Experimental: Regimen B; Patients receive topotecan and carboplatin as in regimen A. Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive treatment as in regimen B; otherwise, patients receive treatment as in regimen A. Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes. Quality of life is assessed at baseline and at the beginning of each course of chemotherapy. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.	Drug: carboplatin; Biological: filgrastim; Drug: topotecan hydrochloride; Radiation: WBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
response rate	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Time Frame
overall survival	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Bryce AH, Mattar B, Hillman SL, Adjei AA, Kugler JW, Rowland K Jr, Wender DB, Soori G, Perez EA, Jett JR. Phase II trial of oral topotecan and intravenous carboplatin with G-CSF support in previously untreated patients with extensive stage small cell lung cancer: A North Central Cancer Treatment Group Study. Am J Clin Oncol. 2010 Aug;33(4):353-7. doi: 10.1097/COC.0b013e3181b0c27f.

Study record dates

Study Major Dates

• Study Start: November 1, 2001
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: June 27, 2003
• First Posted (Estimate): June 30, 2003

Study Record Updates

• Last Update Posted (Estimate): December 7, 2016
• Last Update Submitted That Met QC Criteria: December 5, 2016
• Last Verified: December 1, 2016

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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Carboplatin; Topotecan
• Other Study ID Numbers: NCCTG-N0027; NCI-2012-02441 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000069147 (Registry Identifier: PDQ (Physician Data Query))