A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer.

Authors

• Maha Hussain
• Dana Rathkopf
• Glenn Liu
• Andrew Armstrong
• Wm Kevin Kelly
• Anna Ferrari
• John Hainsworth
• Adarsh Joshi
• Rebecca R Hozak
• Ling Yang
• Jonathan D Schwartz
• Celestia S Higano

Publication/Presentation Date

9-1-2015

Abstract

BACKGROUND: Cixutumumab, a human monoclonal antibody (HuMAb), targets the insulin-like growth factor receptor. Ramucirumab is a recombinant HuMAb that binds to vascular endothelial growth factor receptor-2. A non-comparative randomised phase II study evaluated cixutumumab or ramucirumab plus mitoxantrone and prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC).

PATIENTS AND METHODS: Men with progressive mCRPC during or after docetaxel therapy received mitoxantrone 12 mg/m(2) on day 1 and prednisone 5mg twice daily and were randomised 1:1 to receive either cixutumumab or ramucirumab 6 mg/kg intravenously weekly in a 21-day cycle. Primary end-point was composite progression-free survival (cPFS). Secondary end-points included safety, response, radiographic progression-free survival (PFS) and overall survival (OS). Sample size was based on a 50% increase in median cPFS from 2.6 (MP) to 3.9 months (either combination).

RESULTS: 132 men were treated (66 per arm). Median cPFS was 4.1 months (95% confidence interval (CI), 2.2-5.6) for cixutumumab and 6.7 months (95% CI, 4.5-8.3) for ramucirumab. Median time to radiographic progression was 7.5 months for cixutumumab and 10.2 months for ramucirumab, with a median OS of 10.8 and 13.0 months, respectively. Fatigue was the most frequent adverse event (AE). Incidence of most non-haematologic grade 3-4 AEs was < 10% on both arms. Grade 3 cardiac dysfunction occurred in 7.6% of patients on ramucirumab.

CONCLUSION: Combinations of cixutumumab or ramucirumab plus MP were feasible and associated with moderate toxicities in docetaxel-pretreated men with mCRPC. Of the two regimens, the ramucirumab regimen is worthy of further testing based on the observed cPFS relative to the historical control.

Volume

51

Issue

13

First Page

1714

Last Page

1724

ISSN

1879-0852

Published In/Presented At

Hussain, M., Rathkopf, D., Liu, G., Armstrong, A., Kelly, W. K., Ferrari, A., Hainsworth, J., Joshi, A., Hozak, R. R., Yang, L., Schwartz, J. D., & Higano, C. S. (2015). A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer. European journal of cancer (Oxford, England : 1990), 51(13), 1714–1724. https://doi.org/10.1016/j.ejca.2015.05.019

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

26082390

Department(s)

Administration and Leadership

Document Type

Article