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

November 6, 2007
September 23, 2014
January 2008
August 2011   (final data collection date for primary outcome measure)
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.
Incidence of grade 4 neutropenia or grades 3-4 febrile neutropenia episodes during concurrent chemoradiotherapy as assessed by NCI CTCAE v 3.0
Complete list of historical versions of study NCT00554463 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Incidence of grade 4 neutropenia or grades 3-4 febrile neutropenia episodes during adjuvant chemotherapy as assessed by NCI CTCAE v 3.0
  • Incidence of dose modifications or treatment delays
  • Incidence of esophagitis, pneumonitis, and other non-hematological adverse events as assessed by NCI CTCAE v 3.0
  • Incidence of grade 4 thrombocytopenia
  • Median and the 2-year rates of progression-free and overall survival
Not Provided
Not Provided
 
G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer
A Phase II Trial of Combined Modality Therapy With Growth Factor Support for Patients With Limited Stage Small Cell Lung Cancer

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Lung Cancer
  • 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).
Experimental: Combined Modality Therapy with Growth Factor Support
Radiation therapy, concurrent chemotherapy and Filgrastim followed by adjuvant chemotherapy and Pegfilgrastim
Interventions:
  • Biological: Filgrastim
  • Biological: Pegfilgrastim
  • Drug: Concurrent chemotherapy
  • Drug: Adjuvant chemotherapy
  • Radiation: radiation therapy
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
5
Not Provided
August 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00554463
RTOG 0623, CDR0000574000, NCI-2009-00742
Yes
Radiation Therapy Oncology Group
Radiation Therapy Oncology Group
  • National Cancer Institute (NCI)
  • Cancer and Leukemia Group B
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
Radiation Therapy Oncology Group
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP