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G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00554463
First received: November 6, 2007
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Colony-stimulating factors, such as G-CSF or pegfilgrastim, may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of chemotherapy and radiation therapy.

PURPOSE: This phase II trial is studying G-CSF and pegfilgrastim to see how well they work in treating neutropenia in patients undergoing combination chemotherapy and radiation therapy for limited stage small cell lung cancer.


Condition Intervention Phase
Lung Cancer
Biological: Filgrastim
Biological: Pegfilgrastim
Drug: Concurrent chemotherapy
Drug: Adjuvant chemotherapy
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: A Phase II Trial of Combined Modality Therapy With Growth Factor Support for Patients With Limited Stage Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Incidence of Grade 4 Neutropenia or Grades 3-4 Febrile Neutropenia Episodes During Concurrent Chemoradiotherapy as Assessed by NCI CTCAE v 3.0 (Common Terminology Criteria for Adverse Events) [ Time Frame: At the completion of all treatment, approximately 80 days ] [ Designated as safety issue: Yes ]
    This study stopped accrual early with 5 accrued out of 44 planned, therefore no analyses were performed.


Secondary Outcome Measures:
  • Incidence of Grade 4 Neutropenia or Grades 3-4 Febrile Neutropenia Episodes During Adjuvant Chemotherapy as Assessed by NCI CTCAE v 3.0 [ Time Frame: At the completion of all treatment, approximately 80 days ] [ Designated as safety issue: Yes ]
  • Incidence of Dose Modifications or Treatment Delays [ Time Frame: At the completion of all treatment, approximately 80 days ] [ Designated as safety issue: Yes ]
  • Incidence of Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events as Assessed by NCI CTCAE v 3.0 [ Time Frame: At the completion of all treatment, approximately 80 days ] [ Designated as safety issue: Yes ]
  • Incidence of Grade 4 Thrombocytopenia [ Time Frame: At the completion of all treatment, approximately 80 days ] [ Designated as safety issue: Yes ]
  • Median and 2-year Rates of Progression-free and Overall Survival [ Time Frame: After all patients have been potentially followed for 2 years ] [ Designated as safety issue: No ]

Enrollment: 5
Study Start Date: January 2008
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Combined Modality Therapy with Growth Factor Support
Radiation therapy, concurrent chemotherapy and Filgrastim followed by adjuvant chemotherapy and Pegfilgrastim
Biological: Filgrastim
5mcg/kg/day subcutaneously on days 4-13 and 25-34 after each concurrent chemotherapy cycle for a total of 20 doses.
Biological: Pegfilgrastim
6 mg subcutaneously on day 4 of each adjuvant chemotherapy cycle.
Drug: Concurrent chemotherapy

Beginning day 1 of radiation threapy (+/- 24 hours), repeat cycle every 3 weeks for two cycles:

Day 1: Cisplatin, 60 mg/m^2 i.v.; Days 1-3: Etoposide, 120 mg/m^2 i.v.

Drug: Adjuvant chemotherapy

Cycle 1: Day 43: Cisplatin, 60 mg/m^2 i.v. and Etoposide, 120 mg/m^2 i.v.; Days 44 & 45: Etoposide, 120 mg/m^2 i.v.

Cycle 2: Day 64: Cisplatin, 60 mg/m^2 i.v. and Etoposide, 120 mg/m^2; Days 65 & 66: Etoposide, 120 mg/m^2 i.v.

Radiation: radiation therapy
A total of 61.2 Gy in 5 weeks: 1.8 Gy daily x 5 week, for 3 weeks (days 1-16); 1.8 Gy, BID, in 4th week (days 17-20) with off cord boost in p.m.; Off-cord boost, 1.8 Gy BID, in 5th week (days 21-25).

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the safety and efficacy of filgrastim (G-CSF) in reducing grade 4 neutropenia or grades 3-4 febrile neutropenia in patients with limited stage small cell lung cancer treated with radiotherapy and concurrent chemotherapy comprising cisplatin and etoposide.

Secondary

  • To evaluate the safety and efficacy of pegfilgrastim in reducing grade 4 neutropenia or grades 3-4 febrile neutropenia in patients treated with adjuvant chemotherapy comprising cisplatin and etoposide.
  • To estimate the incidence of dose modifications or treatment delays in patients treated with this regimen.
  • To estimate the incidence of esophagitis, pneumonitis, and other non-hematological adverse events in patients treated with this regimen.
  • To estimate the incidence of grade 4 thrombocytopenia in patients treated with this regimen.
  • To estimate the median and two-year rate of progression-free and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients undergo thoracic radiotherapy once daily on days 1-5 of weeks 1-3 and twice daily on days 1-5 of weeks 4 and 5 for a total of 16 fractions. Patients also receive concurrent chemotherapy comprising cisplatin IV on day 1 and etoposide IV on days 1-3. Chemotherapy repeats every 3 weeks for 2 courses. Patients receive filgrastim (G-CSF) subcutaneously (SC) on days 4-13 and 25-34.

After completion of chemoradiotherapy, patients receive adjuvant chemotherapy comprising cisplatin IV on day 1 and etoposide IV on days 2 and 3. Adjuvant therapy repeats every 21 days for up to 2 courses in the absence of disease progression or unacceptable toxicity. Patients also receive pegfilgrastim SC on day 4 of each course of adjuvant therapy.

After completion of study therapy, patients are followed every 3 months for one year, every 6 months for 2-3 years, and then annually for up to 5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed small cell carcinoma of the lung

    • Limited stage disease, defined as any of the following:

      • Tumor confined to one hemithorax
      • T4 tumor not based on malignant pleural effusion
      • N3 disease not based on contralateral supraclavicular involvement
  • No complete tumor resection
  • Measurable or evaluable disease
  • Pleural effusion allowed provided the following conditions are present:

    • Effusion is too small to tap under CT guidance and is not evident on chest x-ray
    • Effusion appears only after a thoracotomy or other invasive procedure
  • Must have certification by a Radiation Oncologist that the tumor can be encompassed by limited radiotherapy fields without significantly compromising pulmonary function
  • No distant metastases

PATIENT CHARACTERISTICS:

  • Zubrod performance status 0-1
  • ANC (absolute neutrophil count) ≥ 1,800 cells/mm³
  • Platelet count ≥ 100,000 cells/mm³
  • Hemoglobin ≥ 10.0 g/dL (transfusion or other intervention to achieve hemoglobin ≥ 8.0 g/dL allowed)
  • Total bilirubin ≤ 1.5 mg/dL
  • AST (aspartate aminotransferase) or ALT (alanine amino transferase ) ≤ 2 times the upper limit of normal (ULN)
  • Alkaline phosphatase < 2.5 times ULN (< 5 times ULN if judged by the investigator to be related to liver metastases)
  • Serum creatinine ≤ 1.5 mg/dL
  • Creatinine clearance ≥ 50 mL/min
  • FEV1 (Forced Expiratory Volume) obtained pre- or post-bronchodilator must be ≥ 1.5 liters/second
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 60 days after the last study treatment
  • No prior invasive malignancy, except non-melanomatous skin cancer or other micro-invasive malignancy, or carcinoma in situ of the breast, oral cavity, or cervix, unless the patient has been disease-free for a minimum of 3 years
  • No weight loss > 5% for any reason within the past 3 months
  • No severe, active comorbidity, defined as follows:

    • Unstable angina and/or congestive heart failure requiring hospitalization within the past 6 months
    • Transmural myocardial infarction within the past 6 months
    • Acute bacterial or fungal infection requiring intravenous antibiotics
    • Chronic Obstructive Pulmonary Disease exacerbation with FEV1 (forced expiratory volume) < 1.5 liters/second or other respiratory illness requiring hospitalization or precluding study therapy within the past 30 days
    • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
    • AIDS (HIV testing not required for entry into this protocol)
  • No prior allergic reaction to the study drugs

PRIOR CONCURRENT THERAPY:

  • No prior systemic chemotherapy for lung cancer

    • Prior chemotherapy for a different cancer is allowed, provided it was completed ≥ 5 years prior to registration
  • No prior radiotherapy to the region of the study cancer that would result in overlap of radiotherapy fields
  • No concurrent intensity-modulated radiotherapy
  • No concurrent amifostine
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00554463

Locations
United States, Florida
University of Florida Shands Cancer Center
Gainesville, Florida, United States, 32610-0232
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Kentucky
Lucille P. Markey Cancer Center at University of Kentucky
Lexington, Kentucky, United States, 40536-0093
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Montana
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
United States, Nebraska
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
United States, Ohio
McDowell Cancer Center at Akron General Medical Center
Akron, Ohio, United States, 44307
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, United States, 44309-2090
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, United States, 45267
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
Salem, Ohio, United States, 44460
Cancer Treatment Center
Wooster, Ohio, United States, 44691
United States, Pennsylvania
McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
Reading, Pennsylvania, United States, 19612-6052
United States, Wisconsin
Veterans Affairs Medical Center - Milwaukee
Milwaukee, Wisconsin, United States, 53295
Sponsors and Collaborators
Radiation Therapy Oncology Group
Cancer and Leukemia Group B
Investigators
Principal Investigator: Rogerio C. Lilenbaum, MD Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
Study Chair: Ritsuko U. Komaki, MD, FACR M.D. Anderson Cancer Center
Study Chair: Michael A. Samuels, MD CCOP - Mount Sinai Medical Center
Study Chair: Jeffrey Crawford, MD Duke Cancer Institute
  More Information

Additional Information:
Publications:
Lilenbaum R, Samuels M, Taffaro-Neskey M, et al.: Phase II trial of combined modality therapy (cmt) with myeloid growth factors in patients with locally advanced non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 26 (Suppl 15): A-7567, 2008.

Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00554463     History of Changes
Other Study ID Numbers: RTOG 0623, CDR0000574000, NCI-2009-00742
Study First Received: November 6, 2007
Results First Received: September 23, 2014
Last Updated: September 23, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
limited stage small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Small Cell Lung Carcinoma
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Mitogens
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 25, 2014