A Phase II Study of the Safety, Efficacy and Pharmacokinetics of VX-710 in Combination With Doxorubicin and Vincristine in Patients With Small Cell Lung Cancer (SCLC)

OBJECTIVES: I. Established the safety of VX-710 in combination with doxorubicin and vincristine for the treatment of patients with recurrent small cell lung cancer. II. Characterized the plasma pharmacokinetics of this regimen in patients. III. Established the ability of this regimen to improve the response rate to chemotherapy in patients who relapsed on front-line therapy. IV. Evaluated the multidrug resistance profile of these patients following this treatment regimen.

OUTLINE: This was a multicenter study. Stage I: Patients received VX-710 IV over 72 hours, followed by doxorubicin IV and vincristine IV four hours after initial VX-710. Vincristine was administered at half dose in the first 3-6 patients. If no more than 1 of 6 patients experienced a dose limiting toxicity in the half dose cohort, 3 additional patients received full dose vincristine. The maximum tolerated dose was defined as the dose preceding that at which 2 of 6 patients experienced a dose limiting toxicity. Stage II: Patients received VX-710 IV over 72 hours, followed by doxorubicin IV and full dose vincristine IV four hours after initial VX-710. Treatment continued for up to 6 courses every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients were followed every 3 months for up to 1 year.

PROJECTED ACCRUAL: A minimum of 35 and a maximum of 92 patients was to be accrued for this study.