Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma

L. M. Krug, A. J. Wozniak, H. L. Kindler, R. Feld, M. Koczywas, J. L. Morero, C. P. Rodriguez, H. J. Ross, J. E. Bauman, S. V. Orlov, J. C. Ruckdeschel, A. C. Mita, L. Fein, X. He, R. Hall, T. Kawabe, S. Sharma

Research output: Contribution to journalArticle

15 Scopus citations

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: Chemotherapy naïve patients with unresectable MPM were stratified by histology and performance status, and randomized 2:1 to pemetrexed/cisplatin plus CBP501 25mg/m2 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. ≥. 4. mo; the median PFS was 5.1. mo (95% CI, 3.9, 6.5) vs 3.4. mo (2.5, 6.7). Median OS was 13.3. mo (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.

Original languageEnglish (US)
Pages (from-to)429-434
Number of pages6
JournalLung Cancer
Volume85
Issue number3
DOIs
StatePublished - 2014

Keywords

  • CBP501
  • CDC25C
  • Cisplatin
  • DNA repair
  • Malignant pleural mesothelioma
  • Randomized phase II trial

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Krug, L. M., Wozniak, A. J., Kindler, H. L., Feld, R., Koczywas, M., Morero, J. L., Rodriguez, C. P., Ross, H. J., Bauman, J. E., Orlov, S. V., Ruckdeschel, J. C., Mita, A. C., Fein, L., He, X., Hall, R., Kawabe, T., & Sharma, S. (2014). Randomized phase II trial of pemetrexed/cisplatin with or without CBP501 in patients with advanced malignant pleural mesothelioma. Lung Cancer, 85(3), 429-434. https://doi.org/10.1016/j.lungcan.2014.06.008