Clinical trial NCT00028925: Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer
Official title: Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF (Filgrastim) Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Cancer
Keywords: extensive stage small cell lung cancer
Lead sponsor: Alliance for Clinical Trials in Oncology
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-06-30
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Colony-stimulating factors such as filgrastim may increase the number of immune cells found in bone marrow or peripheral blood and may help a person's immune system recover from the side effects of chemotherapy.

PURPOSE: Phase II trial to compare the effectiveness of combination chemotherapy with or without filgrastim in treating patients who have extensive-stage small cell lung cancer that has not been previously treated.

Detailed description: OBJECTIVES:

* Determine the tolerability of topotecan and carboplatin with or without filgrastim (G-CSF) in patients with extensive stage small cell lung cancer.
* Determine response and survival rates in patients treated with these regimens.

OUTLINE: This is a multicenter study. The first 12 patients are assigned to 1 of 2 treatment regimens (6 per regimen). The next 33 patients receive treatment based on the toxicity experienced by the first 12.

Regimen A:

* Patients receive oral topotecan once daily on days 1-5, carboplatin IV over 30 minutes on day 5, and filgrastim (G-CSF) subcutaneously once daily beginning on day 6 or 7 and continuing for up to 10 days or until blood counts recover.
* Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, or no more than 1 patient experiences an absolute neutrophil count of less than 500/mm3 for more than 5 days, the next 6 patients begin treatment on regimen B. Otherwise, all patients receive treatment as in regimen A.

Regimen B:

* Patients receive topotecan and carboplatin as in regimen A.
* Patients are evaluated after the first 3-week course of chemotherapy. If no patient experiences unacceptable toxicity or febrile neutropenia, the next 33 patients receive treatment as in regimen B; otherwise, patients receive treatment as in regimen A.

Treatment for all patients repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with disease progression limited to CNS only interrupt chemotherapy to have whole-brain radiotherapy (WBRT). Once WBRT is complete, chemotherapy resumes.

Quality of life is assessed at baseline and at the beginning of each course of chemotherapy.

Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 49 patients will be accrued for this study within 13.5 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed extensive stage small cell lung cancer

  * Previously untreated with chemotherapy
  * No mixed histology
* Metastatic disease outside the chest

  * Contralateral supraclavicular or hilar nodes that cannot be included in a single radiation port OR
  * Cytologically proven malignant pleural effusion
* Measurable disease
* No untreated CNS metastases

  * CNS metastases treated with whole-brain radiotherapy (WBRT) allowed after completion of WBRT

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* ECOG 0-2

Life expectancy:

* Not specified

Hematopoietic:

* Absolute neutrophil count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* AST no greater than 5 times upper limit of normal (ULN)
* Alkaline phosphatase no greater than 5 times ULN
* Bilirubin no greater than 1.5 times ULN OR
* Direct bilirubin no greater than ULN

Renal:

* Creatinine no greater than 1.5 times ULN OR
* Creatinine clearance at least 50 mL/min

Cardiovascular:

* No uncontrolled angina pectoris
* No congestive heart failure within the past 3 months unless ejection fraction is greater than 40%
* No uncontrolled cardiac arrhythmias
* No myocardial infarction within the past 3 months

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No clinically significant infection
* No hypersensitivity to E. coli-derived proteins
* No other malignancy within the past 3 years except non-melanoma skin cancer, carcinoma in situ of the cervix, or localized prostate cancer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* See Disease Characteristics
* At least 5 years since prior chemotherapy for another malignancy
* No prior nitrosoureas

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics
* No prior thoracic radiotherapy
* At least 1 day since prior palliative radiotherapy (except to chest)
* No more than 3 fractions to chest for superior vena cava syndrome allowed
* No concurrent radiotherapy (including thoracic radiotherapy)

Surgery:

* More than 3 weeks since prior major surgery

Primary outcomes:
measure: response rate
timeFrame: Up to 5 years
Secondary outcomes:
measure: overall survival
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: CCOP - Scottsdale Oncology Program
state: Arizona
city: Washington
country: United States
facility: MBCCOP-Howard University Cancer Center
state: District of Columbia
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Urbana
country: United States
facility: CCOP - Carle Cancer Center
state: Illinois
city: Cedar Rapids
country: United States
facility: CCOP - Cedar Rapids Oncology Project
state: Iowa
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology
state: Iowa
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Wichita Community Clinical Oncology Program
state: Kansas
city: New Orleans
country: United States
facility: CCOP - Ochsner
state: Louisiana
city: Ann Arbor
country: United States
facility: CCOP - Ann Arbor Regional
state: Michigan
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Cloud
country: United States
facility: CentraCare Health Plaza
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Bismarck
country: United States
facility: Medcenter One Health System
state: North Dakota
city: Fargo
country: United States
facility: CCOP - Merit Care Hospital
state: North Dakota
city: Grand Forks
country: United States
facility: Altru Health Systems
state: North Dakota
city: Toledo
country: United States
facility: CCOP - Toledo Community Hospital Oncology Program
state: Ohio
city: Pittsburgh
country: United States
facility: Allegheny General Hospital
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Regina
country: Canada
facility: Allan Blair Cancer Centre
state: Saskatchewan
Study officials:
affiliation: Mayo Clinic
name: James R. Jett, MD
role: STUDY_CHAIR
References:
citation: Bryce AH, Mattar B, Hillman SL, Adjei AA, Kugler JW, Rowland K Jr, Wender DB, Soori G, Perez EA, Jett JR. Phase II trial of oral topotecan and intravenous carboplatin with G-CSF support in previously untreated patients with extensive stage small cell lung cancer: A North Central Cancer Treatment Group Study. Am J Clin Oncol. 2010 Aug;33(4):353-7. doi: 10.1097/COC.0b013e3181b0c27f.