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- Title
A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb-004) in metastatic soft-tissue sarcomas.
- Authors
Jones, Robin L.; Chawla, Sant P.; Attia, Steven; Schöffski, Patrick; Gelderblom, Hans; Chmielowski, Bartosz; Le Cesne, Axel; Van Tine, Brian A.; Trent, Jonathan C.; Patel, Shreyaskumar; Wagner, Andrew J.; Chugh, Rashmi; Heyburn, John W.; Weil, Susan C.; Wang, Wenquan; Viele, Kert; Maki, Robert G.
- Abstract
<bold>Background: </bold>Ontuxizumab, a humanized monoclonal antibody, targets endosialin (tumor endothelial marker 1 [TEM-1] or CD248), which is expressed on sarcoma cells and is believed to be involved in tumor angiogenesis. This is the first trial to evaluate ontuxizumab in patients with sarcoma.<bold>Methods: </bold>Part 1 was an open-label, dose-finding, safety lead-in: 4, 6, or 8 mg/kg with gemcitabine and docetaxel (G/D; 900 mg/m2 gemcitabine on days 1 and 8 and 75 mg/m2 docetaxel on day 8). In part 2, patients were randomized in a double-blind fashion in 2:1 ratio to ontuxizumab (8 mg/kg) or a placebo with G/D. Randomization was stratified by 4 histological cohorts.<bold>Results: </bold>In part 2 with 209 patients, no significant difference in progression-free survival between ontuxizumab plus G/D (4.3 months; 95% confidence interval [CI], 2.7-6.3 months) and the placebo plus G/D (5.6 months; 95% CI, 2.6-8.3 months) was observed (P = .67; hazard ratio [HR], 1.07; 95% CI, 0.77-1.49). Similarly, there was no significant difference in median overall survival between the 2 groups: 18.3 months for the ontuxizumab plus G/D group (95% CI, 16.2-21.1 months) and 21.1 months for the placebo plus G/D group (95% CI, 14.2 months to not reached; P = .32; HR, 1.23; 95% CI, 0.82-1.82). No significant differences between the treatment groups occurred for any efficacy parameter by sarcoma cohort. The combination of ontuxizumab plus G/D was generally well tolerated.<bold>Conclusions: </bold>Ontuxizumab plus G/D showed no enhanced activity over chemotherapy alone in soft-tissue sarcomas, whereas the safety profile of the combination was consistent with G/D alone.
- Subjects
SARCOMA; DOCETAXEL; THERAPEUTICS; HEMATOPOIESIS; TUMOR markers; THERAPEUTIC use of antimetabolites; THERAPEUTIC use of monoclonal antibodies; THERAPEUTIC use of antineoplastic agents; RESEARCH; RESEARCH methodology; ANTINEOPLASTIC agents; DEOXYCYTIDINE; MONOCLONAL antibodies; EVALUATION research; MEDICAL cooperation; ANTIMETABOLITES; COMPARATIVE studies; RANDOMIZED controlled trials; BLIND experiment; RESEARCH funding; TUMOR antigens; STATISTICAL sampling; LONGITUDINAL method; ANTIGENS
- Publication
Cancer (0008543X), 2019, Vol 125, Issue 14, p2445
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.32084