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Phase II study of CI-980 (NSC 635370) in patients with previously treated advanced soft-tissue sarcomas
S R Patel1, M A Burgess, N E Papadopolous
1Department of Melanoma/Sarcoma Medical Oncology, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
Doxorubicin and ifosfamide are the two most active agents in the treatment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore, important to identify newer drugs with activity against this disease. CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin and blocks cell cycle progression in mitosis. Given its broad spectrum activity against several solid tumor models in vivo, we decided to perform a phase 2 study of this drug in previously treated soft-tissue sarcomas. A total of 18 eligible and evaluable patients were entered in the first stage of the trial. The median age was 53 yrs (range, 17-72). No objective responses have been noted. Six patients had stable disease after a median of 3.5 cycles of chemotherapy while 12 others had progressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m2/d x 3). The median AGC nadir was 1.2/microl(0.1 -4.7) on day 10 and the median platelet nadir was 150,000/microl (31,000-338,000). Twenty cycles were complicated with grade 3-4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade 1 thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one cycle. In conclusion, CI-980 was well tolerated at this dose and schedule but inactive in soft-tissue sarcomas.
Insights
CI-980, a novel mitotic inhibitor, showed no objective responses in patients with advanced soft-tissue sarcomas previously treated with doxorubicin and ifosfamide. While well-tolerated, this drug demonstrated inactivity in this patient population.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Doxorubicin and ifosfamide are standard treatments for soft-tissue sarcomas.
- Limited systemic therapy options exist for patients resistant to these agents.
- Newer drugs with activity against soft-tissue sarcomas are needed.
Purpose of the Study:
- To evaluate the efficacy and safety of CI-980 in patients with soft-tissue sarcomas previously treated with doxorubicin and ifosfamide.
- To determine if CI-980 exhibits anti-tumor activity in this refractory patient group.
Main Methods:
- A Phase 2 clinical trial was conducted.
- 18 eligible patients with advanced soft-tissue sarcomas were enrolled.
- Patients received CI-980 at a dose of 4.5 mg/m2/day for 3 days.
Main Results:
- No objective responses (complete or partial) were observed in any patient.
- Six patients achieved stable disease, while 12 experienced progressive disease.
- The drug was generally well-tolerated, with manageable neutropenia and thrombophlebitis.
Conclusions:
- CI-980 demonstrated inactivity as a treatment for advanced soft-tissue sarcomas in this patient population.
- The drug was well-tolerated at the tested dose and schedule.
- Further investigation of CI-980 in soft-tissue sarcomas is not warranted based on these findings.