A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of monotherapy ontuxizumab (MORAb-004) plus best supportive care in patients with chemorefractory metastatic colorectal cancer Journal Article
| Authors: | Grothey, A.; Strosberg, J. R.; Renfro, L. A.; Hurwitz, H. I.; Marshall, J. L.; Safran, H.; Guarino, M. J.; Kim, G. P.; Hecht, J. R.; Weil, S. C.; Heyburn, J.; Wang, W.; Schweizer, C.; O'Shannessy, D. J.; Diaz, L. A. Jr |
| Article Title: | A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of monotherapy ontuxizumab (MORAb-004) plus best supportive care in patients with chemorefractory metastatic colorectal cancer |
| Abstract: | Purpose: The purpose of this study was to evaluate the safety and efficacy of ontuxizumab (MORAb-004), a monoclonal antibody that interferes with endosialin (tumor endothelial marker-1) function, in patients with chemorefractory metastatic colorectal cancer and to identify a responsive patient population based on biomarkers. Experimental Design: This was a randomized, double-blind, placebo-controlled, phase II study. Patients were randomly assigned in a 2:1 ratio to receive weekly intravenous ontuxizumab (8 mg/kg) or placebo plus best supportive care until progression or unacceptable toxicity. Tissue and blood biomarkers were evaluated for their ability to identify a patient population that was responsive to ontuxizumab. Results: A total of 126 patients were enrolled. No significant difference between the ontuxizumab and placebo groups was evident for the primary endpoint of progression-free survival (PFS), with a median PFS of 8.1 weeks in each group (HR, 1.13; 95% confidence interval, 0.76-1.67; P = 0.53). There were no significant differences between groups for overall survival (OS) or overall response rate (ORR). The most common treatment-emergent adverse events (TEAEs) in the ontuxizumab group (vs. the placebo group, respectively) were fatigue (53.7% vs. 47.5%), nausea (39.0% vs. 35.0%), decreased appetite (34.1% vs. 27.5%), and constipation (28.0% vs. 32.5%). The most common grade 3/4 TEAE in the ontuxizumab group versus placebo was back pain (11.0% vs. 0%). No single biomarker clearly identified patients responsive to ontuxizumab. Conclusions: No benefit with ontuxizumab monotherapy compared with placebo for clinical response parameters of PFS, OS, or ORR was demonstrated. Ontuxizumab was well tolerated. © 2017 AACR. |
| Keywords: | adult; controlled study; human tissue; aged; human cell; major clinical study; overall survival; constipation; fatigue; bevacizumab; placebo; diarrhea; drug dose reduction; drug efficacy; drug safety; monotherapy; nonhuman; side effect; prospective study; biological marker; demography; progression free survival; phase 2 clinical trial; anemia; nausea; randomized controlled trial; vomiting; dehydration; body weight; tumor biopsy; cancer therapy; carcinogenesis; irinotecan; abdominal pain; asthenia; backache; chill; coughing; dyspnea; fever; confidence interval; alkaline phosphatase; urinary tract infection; peripheral edema; lactate dehydrogenase; headache; oxaliplatin; double blind procedure; fluoropyrimidine; disease exacerbation; underweight; blood level; hyperhidrosis; platelet derived growth factor b; decreased appetite; metastatic colorectal cancer; musculoskeletal pain; human; female; priority journal; article; endosialin; morab 004; ontuxizumab; best supportive care |
| Journal Title: | Clinical Cancer Research |
| Volume: | 24 |
| Issue: | 2 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2018-01-15 |
| Start Page: | 316 |
| End Page: | 325 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-17-1558 |
| PROVIDER: | scopus |
| PUBMED: | 29084918 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 February 2018 -- Source: Scopus |
