An open-label, phase 2 study evaluating the efficacy and safety of the anti-IGF-1R antibody cixutumumab in patients with previously treated advanced or metastatic soft-tissue sarcoma or Ewing family of tumours

• Published in: European journal of cancer (1990) Vol. 49; no. 15; pp. 3219 - 3228
• Main Authors: Schöffski, P, Adkins, D, Blay, J.-Y, Gil, T, Elias, A.D, Rutkowski, P, Pennock, G.K, Youssoufian, H, Gelderblom, H, Willey, R, Grebennik, D.O
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-10-2013; Elsevier
• Subjects: Adipocytic sarcoma; Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; Cixutumumab; Disease-Free Survival; Ewing family of tumours; Female; Hematology, Oncology and Palliative Medicine; Humans; Insulin-like growth factor receptor; Leiomyosarcoma; Male; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Metastasis; Pharmacology. Drug treatments; Rhabdomyosarcoma; Sarcoma - drug therapy; Sarcoma, Ewing - drug therapy; Soft-tissue sarcoma; Synovial sarcoma; Treatment Outcome; Tumors; Young Adult; Insulin-like growth factor receptor; Ewing family of tumours; Synovial sarcoma; Soft-tissue sarcoma; Rhabdomyosarcoma; Leiomyosarcoma; Cixutumumab; Adipocytic sarcoma; Antineoplastic agent; Ewing sarcoma; Toxicity; Diseases of the osteoarticular system; Smooth muscle; Monoclonal antibody; Metastasis; Insulin like growth factor; Cancerology; Type 1 insulin-like growth factor receptor; Phase II trial; Family environment; Advanced stage; Biological receptor; Human; Family study; Treatment efficiency; Soft tissue sarcoma; Malignant tumor; Striated muscle disease; Treatment; Cancer
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2013.06.010

Abstract Background Cixutumumab (IMC-A12), a fully human immunoglobulin G1 (IgG1) monoclonal antibody, exerts preclinical activity in several sarcoma models and may be effective for the treatment of these tumours. Methods In this open-label, multicentre, phase 2 study, patients with previously treated advanced or metastatic rhabdomyosarcoma, leiomyosarcoma, adipocytic sarcoma, synovial sarcoma or Ewing family of tumours received intravenous cixutumumab (10 mg/kg) for 1 h every other week until disease progression or discontinuation. The primary end-point was the progression-free survival rate (PFR), defined as stable disease or better at 12 weeks. In each tier of disease histology, Simon’s optimum 2-stage design was applied (PFR at 12 weeks P0 = 20%, P1 = 40%, α = 0.10, β = 0.10). Stage 1 enrolled 17 patients in each disease group/tier, with at least four patients with stable disease or better required at 12 weeks to proceed to stage 2. Results A total of 113 patients were enrolled; all tiers except adipocytic sarcoma were closed after stage 1 due to futility. The 12-week PFR was 12% for rhabdomyosarcoma ( n = 17), 14% for leiomyosarcoma ( n = 22), 32% for adipocytic sarcoma ( n = 37), 18% for synovial sarcoma ( n = 17) and 11% for Ewing family of tumours ( n = 18). Median progression-free survival (weeks) was 6.1 for rhabdomyosarcoma, 6.0 for leiomyosarcoma, 12.1 for adipocytic sarcoma, 6.4 for synovial sarcoma and 6.4 for Ewing family of tumours. Among all patients, the most frequent treatment-emergent adverse events (AEs) were nausea (26%), fatigue (23%), diarrhoea (23%) and hyperglycaemia (20%). Conclusions Patients with adipocytic sarcoma may benefit from treatment with cixutumumab. Cixutumumab treatment was well tolerated, with limited gastrointestinal AEs, fatigue and hyperglycaemia.