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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00554463

Enrollment

Registered

2007-11-07

Start date

2008-01-31

Completion date

2011-08-03

Last updated

2019-05-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer

Keywords

limited stage small cell lung cancer

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.

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.

Interventions

DRUGFilgrastim

5 mcg/kg/day IV (intravenous) days 4-13 and days 25-34 for a total of 20 doses.

DRUGPegfilgrastim

6 mg via subcutaneous injection days 46 and 67

DRUGEtoposide

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.

DRUGCisplatin

Concurrent: 60 mg/m\^2, IV on days 1 and 22. Adjuvant: 60 mg/m\^2, IV on days 43 and 64.

RADIATIONradiation 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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

SUPPORTIVE_CARE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy	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

Measure	Time frame	Description
Number of Patients With Grade 3-4 Febrile Neutropenia During Adjuvant Chemoradiotherapy	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.
Number of Patients With Dose Modifications or Treatment Delays	From start of treatment to end of treatment, for a maximum of 66 days	—
Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events	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.
Number of Patients With Grade 4 Thrombocytopenia	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.
Overall Survival	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.
Progression-free Survival	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Combined Modality Therapy With Growth Factor Support Concurrent radiation therapy, cisplatin, etoposide, and filgrastim followed by adjuvant cisplatin, etoposide, and pegfilgrastim.	5
Total	5

Baseline characteristics

Characteristic	Combined Modality Therapy With Growth Factor Support
Age, Continuous	67 years
Sex: Female, Male Female	4 Participants
Sex: Female, Male Male	1 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	5 / 5
serious Total, serious adverse events	2 / 5

Outcome results

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.

Time frame: From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days