Combination Chemotherapy With or Without Filgrastim in Treating Patients With Previously Untreated Extensive-Stage Small Cell Lung Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2

Conditions: Lung Cancer

Treatments: Radiation: WBRT; Drug: carboplatin; Drug: topotecan hydrochloride; Biological: filgrastim

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00028925

NCI-2012-02441 (Registry Identifier)

NCCTG-N0027

CDR0000069147 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

---

27 participants in 2 patient groups

Regimen A

Experimental group

Description:

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. 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.

Treatment:

Radiation: WBRT

Drug: carboplatin

Biological: filgrastim

Drug: topotecan hydrochloride

Regimen B

Experimental group

Description:

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.

Treatment:

Radiation: WBRT

Drug: carboplatin

Biological: filgrastim

Drug: topotecan hydrochloride