Trial Information

Phase II Study of Sequential Topotecan-Carboplatin-Etoposide in Patients With Extensive Stage Small Cell Lung Cancer

OBJECTIVES:

- Determine the toxicity profile and maximum tolerated dose of sequential topotecan,
carboplatin, and etoposide in patients with chemotherapy-naive extensive stage small
cell lung cancer. (Phase I closed to accrual as of 04/04/2003).

- Determine the response rate and duration of response in patients with treated with this
regimen.

- Determine the failure-free and overall survival of patients treated with this regimen.

- Determine the pharmacokinetics and pharmacodynamics of topotecan and etoposide on this
schedule in these patients.

OUTLINE: This is a dose-escalation, multicenter study of topotecan and etoposide. (Phase I
closed to accrual as of 04/04/2003).

Patients receive oral topotecan on days 1-5, carboplatin IV over 30 minutes on day 6, and
oral etoposide on days 6-10. Treatment continues every 3 weeks for 2 courses in the absence
of disease progression or unacceptable toxicity. Patients with complete response (CR) or
partial response after the second course receive up to 4 additional courses. Patients with
brain metastases at initial presentation undergo whole-brain irradiation before the
chemotherapy regimen. Patients without brain metastases at initial presentation who achieve
CR undergo prophylactic whole-brain irradiation.

Sequential dose escalation of topotecan is followed by sequential dose escalation of
etoposide. Cohorts of 3-6 patients receive escalating doses of topotecan and then etoposide
until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined
as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting
toxicity. (Phase I closed to accrual as of 04/04/2003). In the phase II part of study, an
additional 11-40 patients are accrued to receive topotecan, carboplatin, and etoposide at
the MTD.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A maximum of 50 patients (3-10 for phase I and 11-40 for phase II) will
be accrued for this study. (Phase I closed to accrual as of 04/04/2003)