Combination Chemotherapy and Radiation Therapy in Treating Patients With Limited-Stage Small Cell Lung Cancer

Alliance for Clinical Trials in Oncology

Status and phase: Completed; Phase 2; Phase 1

Conditions: Radiation Toxicity; Lung Cancer; Drug/Agent Toxicity by Tissue/Organ

Treatments: Drug: cisplatin; Drug: paclitaxel; Drug: etoposide; Drug: amifostine trihydrate; Drug: topotecan hydrochloride; Biological: filgrastim; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00006012

NCCTG-N9923

CDR0000068021 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy before, during, and after radiation therapy in treating patients who have limited-stage small cell lung cancer.

Full description

OBJECTIVES:

• Determine the maximum tolerated dose of thoracic radiotherapy administered with cisplatin, etoposide, and amifostine preceded and followed by topotecan and paclitaxel in patients with limited stage small cell lung cancer (phase I closed to accrual as of 5/27/2004).
• Determine the two-year survival of this patient population treated with this regimen.
• Determine the two-year, progression-free local control rate in this patient population treated with this regimen.
• Assess the tolerability of this treatment regimen in these patients.
• Determine the antitumor activity of this regimen in these patients.
• Determine the overall survival and overall time to progression in this patient population treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of thoracic radiotherapy (TRT).

Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 5. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 24 hours after the last dose of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 2 courses.

After 2 courses of topotecan and paclitaxel, patients undergo TRT twice daily for 5 consecutive days for 5 weeks. During TRT, patients receive cisplatin IV, oral etoposide, and amifostine SC daily prior to TRT.

At 4 weeks after completion of TRT, patients receive 2 additional courses of topotecan, paclitaxel, and G-CSF every 3 weeks followed by prophylactic cranial irradiation.

Cohorts of 3-6 patients receive escalating doses of TRT until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity (phase I closed to accrual as of 5/27/2004).

Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 3-73 patients will be accrued for this study (phase I closed to accrual as of 5/27/2004).

Enrollment: 73 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed small cell lung cancer

• Limited disease confined to one hemithorax, the ipsilateral supraclavicular fossa, and encompassable within tolerable thoracic radiotherapy field

  • Minimal pleural effusions (i.e., blunting of the costophrenic angle on chest x-ray or a small effusion on CT scan) allowed

• Measurable disease

  • At least one lesion accurately measured in at least 1 dimension with longest diameter at least 20 mm

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-2

Life expectancy:

• At least 12 weeks

Hematopoietic:

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

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• AST no greater than 3 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Pulmonary:

• FEV_1 at least 40% of predicted AND at least 1 liter

Other:

• No uncontrolled infection
• No other severe underlying diseases
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or noninvasive carcinomas (carcinoma in situ)
• No grade 2 or greater peripheral neuropathy
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No hypersensitivity to E.coli-derived proteins, filgrastim (G-CSF), or any excipients of G-CSF

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• No prior hemithorax radiotherapy

Surgery

• Not specified

Other

• No prior therapy for small cell lung cancer

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

---

73 participants in 1 patient group

topotecan + paclitaxel + filgrastim + TRT + radiation

Experimental group

Description:

Patients receive topotecan IV on days 1-5 and paclitaxel IV over 3 hours on day 5. Patients receive filgrastim (G-CSF) subcutaneously (SC) daily beginning 24 hours after the last dose of chemotherapy and continuing until blood counts recover. Treatment repeats every 3 weeks for 2 courses. After 2 courses of treatment, patients undergo TRT twice daily for 5 consecutive days for 5 weeks. During TRT, patients receive cisplatin IV, oral etoposide, and amifostine SC daily prior to TRT. At 4 weeks after completion of TRT, patients receive 2 additional courses of topotecan, paclitaxel, and G-CSF every 3 weeks followed by prophylactic cranial irradiation. Patients are followed every 3 months for 1 year, every 4 months for 1 year, and then every 6 months for 3 years.

Treatment:

Drug: topotecan hydrochloride

Drug: etoposide

Drug: paclitaxel

Radiation: radiation therapy

Drug: cisplatin

Drug: amifostine trihydrate

Biological: filgrastim