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

• ClinicalTrials.gov Identifier: NCT00554463
• Recruitment Status: Completed
• First Posted: November 7, 2007
• Results First Posted: September 29, 2014
• Last Update Posted: May 29, 2019
• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI); Cancer and Leukemia Group B
• Information provided by (Responsible Party): Radiation Therapy Oncology Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Lung Cancer	Drug: Filgrastim; Drug: Pegfilgrastim; Drug: Etoposide; Drug: Cisplatin; Radiation: radiation therapy	Phase 2

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.

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: January 2008
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: August 3, 2011

Arms and Interventions

Arm

Intervention/treatment

Experimental: Combined Modality Therapy with Growth Factor Support; Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim.

Drug: Filgrastim; 5 mcg/kg/day IV (intravenous) days 4-13 and days 25-34 for a total of 20 doses.; Drug: Pegfilgrastim; 6 mg via subcutaneous injection days 46 and 67; Drug: Etoposide; Concurrent: 120 mg/m^2, IV on days 1-3 and days 22-24. Adjuvant: 120 mg/m^2, IV on days 43-45 and days 65-66.; Drug: Cisplatin; Concurrent: 60 mg/m^2, IV on days 1 and 22. Adjuvant: 60 mg/m^2, IV on days 43 and 64.; Radiation: radiation therapy; A total of 61.2 Gy in 5 weeks: Once-daily 1.8 Gy fractions for 15 fractions over 3 weeks beginning on day 1 of chemotherapy, then twice-daily 1.8 Gy fractions for 10 fractions over 2 weeks.

Outcome Measures

Primary Outcome Measures :

1. Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy [ Time Frame: From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days ]
   Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. No testing was done due to early study termination.

Secondary Outcome Measures :

1. Number of Patients With Grade 3-4 Febrile Neutropenia During Adjuvant Chemoradiotherapy [ Time Frame: From the start to the end of adjuvant chemotherapy, a maximum of 24 days ]
   Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
2. Number of Patients With Dose Modifications or Treatment Delays [ Time Frame: From start of treatment to end of treatment, for a maximum of 66 days ]
3. Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events [ Time Frame: From registration to last follow-up, a maximum of 32.9 months ]
   Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. No testing was done due to early study termination.
4. Number of Patients With Grade 4 Thrombocytopenia [ Time Frame: From registration to last follow-up, a maximum of 32.9 months ]
   Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE.
5. Overall Survival [ Time Frame: From registration to last follow-up, a maximum of 32.9 months ]
   Overall survival time is defined as time from registration/randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. Due to early termination with few patients, only counts of events have been calculated.
6. Progression-free Survival [ Time Frame: From registration to last follow-up, a maximum of 32.9 months ]
   Progression is defined as any failure per Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Progression-free survival time is defined as time from registration to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. Due to early termination with few patients, only counts of events have been calculated.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

National Cancer Institute (NCI)

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

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
• Other Study ID Numbers: RTOG 0623; CDR0000574000; NCI-2009-00742 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
• First Posted: November 7, 2007
• Results First Posted: September 29, 2014
• Last Update Posted: May 29, 2019
• Last Verified: May 2019

Keywords provided by Radiation Therapy Oncology Group:

limited stage small cell lung cancer

Additional relevant MeSH terms:

Lung Neoplasms; Small Cell Lung Carcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Etoposide; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action