Phase II Study of Aerosolized Liposomal 9-Nitro-20 (S)- Camptothecin (L9NC) in Patients With Metastatic or Recurrent Cancer of the Endometrium
RATIONALE: Camptothecin (CPT) is a plant alkaloid isolated from Camptotheca acuminata
in 1966. As a topoisomerase I inhibitor, it has powerful anticancer properties and has been
used clinically in the treatment of a variety of cancers. It possesses significant
toxicity, especially involving the bone marrow and gastrointestinal tract that has limited
its use. Derivatives of 20-(S)-camptothecin have been made to increase the aqueous
solubility of these compounds and/or modify the A-ring to increase membrane association.
The 9-nitrocamptothecin (9-NC) derivative to be used in this study is insoluble in water,
but has demonstrated potent antitumor effects in mice and antitumor effect in humans.
However, the therapeutic index is low. In order to increase the therapeutic index, a
liposomal formulation has been developed, which can be administered as an aerosol. In
humans, dose of 0.52 mg/m2/day 5 days per weeks for eight 8 weeks of a 10 week course were
well tolerated in the Phase I study. Partial responses were noted in patients with
endometrial cancers. The recommended starting dose of L9NC in the Phase II study is 0.52
mg/m2/day to be administered once a day by aerosol (mouth-only breathing) for five
consecutive days per week x 8 weeks followed by a 2 week rest. Courses are 10 weeks. This
dose corresponds to approximately 1/6 of the MTD of oral 9-NC administered to untreated
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall response rate (complete and partial responses).Activity will be calculated as the proportion of pts with responsive disease & the 95% confidence interval for response.
Claire Verschraegen, MD
University of New Mexico
United States: Institutional Review Board
|University of New Mexico||Albuquerque, New Mexico 87131|