Clinical trial NCT00554463: G-CSF and Pegfilgrastim in Treating Neutropenia in Patients Undergoing Radiation Therapy and Chemotherapy for Limited Stage Small Cell Lung Cancer
Official title: A Phase II Trial of Combined Modality Therapy With Growth Factor Support for Patients With Limited Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: limited stage small cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: Cancer and Leukemia Group B
First posted: 2007-11-07
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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

Primary outcomes:
measure: Number of Patients With Grade 3-4 Febrile Neutropenia During Concurrent Chemoradiotherapy
timeFrame: From start of treatment to end of concurrent chemoradiation, for a maximum of 45 days
Secondary outcomes:
measure: Number of Patients With Grade 3-4 Febrile Neutropenia During Adjuvant Chemoradiotherapy
timeFrame: From the start to the end of adjuvant chemotherapy, a maximum of 24 days
measure: Number of Patients With Dose Modifications or Treatment Delays
timeFrame: From start of treatment to end of treatment, for a maximum of 66 days
measure: Number of Patients With Grade 3+ Esophagitis, Pneumonitis, and Other Non-hematological Adverse Events
timeFrame: From registration to last follow-up, a maximum of 32.9 months
measure: Number of Patients With Grade 4 Thrombocytopenia
timeFrame: From registration to last follow-up, a maximum of 32.9 months
measure: Overall Survival
timeFrame: From registration to last follow-up, a maximum of 32.9 months
measure: Progression-free Survival
timeFrame: From registration to last follow-up, a maximum of 32.9 months
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Miami Beach
country: United States
facility: CCOP - Mount Sinai Medical Center
state: Florida
city: Lexington
country: United States
facility: Lucille P. Markey Cancer Center at University of Kentucky
state: Kentucky
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Salem
country: United States
facility: Cancer Research UK Medical Oncology Unit at Churchill Hospital & Weatherall Institute of Molecular Medicine - Oxford
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Reading
country: United States
facility: McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center
state: Pennsylvania
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee
state: Wisconsin
Study officials:
affiliation: Mount Sinai Comprehensive Cancer Center at Mount Sinai Medical Center
name: Rogerio C. Lilenbaum, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: M.D. Anderson Cancer Center
name: Ritsuko U. Komaki, MD, FACR
role: STUDY_CHAIR
affiliation: CCOP - Mount Sinai Medical Center
name: Michael A. Samuels, MD
role: STUDY_CHAIR
affiliation: Duke Cancer Institute
name: Jeffrey Crawford, MD
role: STUDY_CHAIR
References:
citation: Lilenbaum R, Samuels M, Taffaro-Neskey M, Cusnir M, Pizzolato J, Blaustein A. Phase II trial of combined modality therapy with myeloid growth factor support in patients with locally advanced non-small cell lung cancer. J Thorac Oncol. 2010 Jun;5(6):837-40. doi: 10.1097/JTO.0b013e3181d6e141.