Trial Information

Phase I-II Study of Topotecan and Paclitaxel Followed by High-Dose Thoracic Radiation Therapy With Concomitant Cisplatin/Etoposide and Amifostine in Limited-Stage Small Cell Lung Cancer

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).