L M Krug1, A J Wozniak2, H L Kindler3, R Feld4, M Koczywas5, J L Morero6, C P Rodriguez7, H J Ross8, J E Bauman9, S V Orlov10, J C Ruckdeschel11, A C Mita12, L Fein13, X He14, R Hall14, T Kawabe15, S Sharma16. 1. Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. Electronic address: krugl@mskcc.org. 2. Karmanos Cancer Center, Detroit, MI, USA. 3. University of Chicago, Chicago, IL, USA. 4. Princess Margaret Hospital, Toronto, ON, Canada. 5. City of Hope Cancer Center, Duarte, CA, USA. 6. Hospital Maria Ferrer, Buenos Aires, Argentina. 7. University of Washington, Seattle, WA, USA. 8. Mayo Clinic Arizona, Scottsdale, AZ, USA. 9. University of New Mexico, Albuquerque, NM, USA. 10. St. Petersburg Medical University, St. Petersburg, Russia. 11. Intermountain Healthcare, Salt Lake City, UT, USA. 12. Cedars-Sinai Medical Center, Los Angeles, CA, USA. 13. Centro Oncologico de Rosario, Rosario, Argentina. 14. ICON Clinical Research, North Wales, PA, USA. 15. CanBas Co., Ltd., Numazu City, Shizuoka, Japan. 16. Huntsman Cancer Institute, Salt Lake City, UT, USA.
Abstract
BACKGROUND: CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatin cytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin. METHODS:Chemotherapynaïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25mg/m(2) IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months. RESULTS:65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS≥4mo; the median PFS was 5.1mo (95% CI, 3.9, 6.5) vs 3.4mo (2.5, 6.7). Median OS was 13.3mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501. CONCLUSIONS: While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM.
RCT Entities:
BACKGROUND: CBP501, a synthetic duodecapeptide, increases cisplatin influx into tumor cells through an interaction with calmodulin enhancing cisplatincytotoxicity, and effects cell cycle progression by abrogating DNA repair at the G2 checkpoint. In phase I clinical trials of CBP501 alone or in combination with cisplatin, the most common toxicity was infusion-related urticaria. Activity of CBP501 plus cisplatin was observed in patients with ovarian cancer and mesothelioma, including some patients previously treated with cisplatin. METHODS: Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25mg/m(2) IV (Arm A) or pemetrexed/cisplatin alone (Arm B). The primary endpoint was progression free survival (PFS) at 4 months. RESULTS: 65 patients were randomized, and 63 were treated. Patient characteristics in the two arms were balanced. Based on independent radiology review of the treated population, 25/40 patients (63%) in Arm A and 9/23 (39%) in Arm B had PFS≥4mo; the median PFS was 5.1mo (95% CI, 3.9, 6.5) vs 3.4mo (2.5, 6.7). Median OS was 13.3mo (9.2, 16.3) in Arm A and 12.8 (6.5, 16.1) in Arm B. Adverse events were not different than expected from standard chemotherapy, and comparable in the two arms, aside from infusion reactions which occurred in 70% of patients treated with CBP501. CONCLUSIONS: While this randomized phase II trial met its primary endpoint of PFS at 4 months, other parameters such as response rate and overall survival suggest that the addition of CBP501 does not improve the efficacy of standard chemotherapy for MPM.
Authors: Jennifer L Beebe-Dimmer; Jon P Fryzek; Cecilia L Yee; Tapashi B Dalvi; David H Garabrant; Ann G Schwartz; Shirish Gadgeel Journal: Clin Epidemiol Date: 2016-10-26 Impact factor: 4.790
Authors: Patrick M Forde; Valsamo Anagnostou; Zhuoxin Sun; Suzanne E Dahlberg; Hedy L Kindler; Noushin Niknafs; Thomas Purcell; Rafael Santana-Davila; Arkadiusz Z Dudek; Hossein Borghaei; Mara Lanis; Zineb Belcaid; Kellie N Smith; Archana Balan; James R White; Christopher Cherry; I K Ashok Sivakumar; Xiaoshan M Shao; Hok Yee Chan; Dipika Singh; Sampriti Thapa; Peter B Illei; Drew M Pardoll; Rachel Karchin; Victor E Velculescu; Julie R Brahmer; Suresh S Ramalingam Journal: Nat Med Date: 2021-11-08 Impact factor: 53.440