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

Lung Cancer Clinical Trial

Official title:

A Phase II Trial of Combined Modality Therapy With Growth Factor Support for Patients With Limited Stage Small Cell Lung Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00554463
• Other study ID #: RTOG 0623
• Secondary ID: CDR0000574000NCI
• Status: Completed
• Phase: Phase 2
• Start date: January 2008
• Est. completion date: August 3, 2011

Study information

• Verified date: May 2019
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: August 3, 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms
• Small Cell Lung Carcinoma

Intervention

Drug:
• Filgrastim
5 mcg/kg/day IV (intravenous) days 4-13 and days 25-34 for a total of 20 doses.
• Pegfilgrastim
6 mg via subcutaneous injection days 46 and 67
• 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.
• 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.

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford	Salem	Ohio
United States	Cancer Treatment Center	Wooster	Ohio

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	Cancer and Leukemia Group B, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy	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.	From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days
Secondary	Number of Patients With Grade 3-4 Febrile Neutropenia During Adjuvant Chemoradiotherapy	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.	From the start to the end of adjuvant chemotherapy, a maximum of 24 days
Secondary	Number of Patients With Dose Modifications or Treatment Delays		From start of treatment to end of treatment, for a maximum of 66 days
Secondary	Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events	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.	From registration to last follow-up, a maximum of 32.9 months
Secondary	Number of Patients With Grade 4 Thrombocytopenia	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.	From registration to last follow-up, a maximum of 32.9 months
Secondary	Overall Survival	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.	From registration to last follow-up, a maximum of 32.9 months
Secondary	Progression-free Survival	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.	From registration to last follow-up, a maximum of 32.9 months