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 Journal Article
| Authors: | 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. |
| Article Title: | 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 |
| Abstract: | 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/m2 on day 1 and prednisone 5 mg 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. © 2015 The Authors. |
| Keywords: | adult; cancer survival; controlled study; aged; major clinical study; overall survival; prednisone; constipation; fatigue; neutropenia; cancer combination chemotherapy; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; drug withdrawal; hypertension; treatment duration; anorexia; prostate specific antigen; progression free survival; multiple cycle treatment; phase 2 clinical trial; anemia; leukopenia; randomized controlled trial; stomatitis; thrombocytopenia; dehydration; interleukin 8; cancer mortality; cixutumumab; docetaxel; arthralgia; backache; dyspnea; hyperglycemia; prostate cancer; multicenter study; mitoxantrone; vasculotropin a; peripheral edema; open study; heart left ventricle ejection fraction; placental growth factor; ecchymosis; castration resistant prostate cancer; chemotherapy induced nausea and vomiting; ramucirumab; human; male; priority journal; article |
| Journal Title: | European Journal of Cancer |
| Volume: | 51 |
| Issue: | 13 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2015-09-01 |
| Start Page: | 1714 |
| End Page: | 1724 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2015.05.019 |
| PROVIDER: | scopus |
| PUBMED: | 26082390 |
| PMCID: | PMC5024789 |
| DOI/URL: | |
| Notes: | Export Date: 2 September 2015 -- Source: Scopus |
