Entry Detail
| General information | |
| Database: | DB00585 |
| Objective: | They explored sorafenib activity in patients with relapsed and unresectable osteosarcoma. |
| Authors: | Grignani G, |
| Title: | a phase II trial of sorafenib in relapsed and unresectable highgrade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. |
| Journal: | Ann Oncol. |
| Year: | 2012 |
| PMID: | 21527590 |
| Trial Design | |
| Clinical Trial Id: | NA |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | osteosarcoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a phase II trial |
| Key Patients Feature: | Eligible patients had the following characteristics: age >17 years; diagnosis confirmed histologically and revietheyd centrally; prior treatment(completed >4 weeks before trial entry) consisted of standard highgradeosteosarcoma chemotherapy agents including doxorubicin, cisplatin, highdose methotrexate, and ifosfamide; metastatic relapsed and unresectableprogressive disease (PD); Eastern Cooperative Oncology Groupperformance status ¡ê2 with a life expectancy >3 months; adequate renal, hepatic, and hemopoietic function. Additionally, they required normal orcontrolled blood pressure, as well as surgery and/or radiotherapycompletion at least 1 month before enrollment. Later, the protocol wasamended to enroll patients >14 years and those treated for relapsedosteosarcoma with up to two lines of treatment (e.g. gemcitabine, Taxotere , SanofiAventis US, Bridgewater, NJ or monoclonal antibodyagainst IGFIR) |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts were eligible to receive 400 mg of sorafenib twice daily until progression or unacceptable toxicity |
| Primary End Point: | progression free survival (PFS) at 4 months. |
| Secondary End Point: | PFS, overall survival (OS), clinical benefit rate (CBR) |
| Patients Number: | 35 |
| Trial Results | |
| DLT_MTD: | The overallincidence of sorafenibrelated adverse events was 78%. Ingeneral, drugrelated adverse events were limited to grade 1 or2. they noted the following grade 3 and 4 toxic effects: anemia 2 (6%), thrombocytopenia 2 (6%), nausea 1 (3%), asymptomaticlipase G4 increase 1 (3%), abdominal cramps 1 (3%), oralmucositis 1 (3%), hand-foot skin reaction 3 (9%) and 1 (3%)skin metastasis bleeding (after a minor trauma) |
| Objective Response Rate: | PFS at 4 months was 46% (95% CI 28% to 63%). Median PFS and OSwere 4 (95% CI 2-5) and 7 (95% CI 7-8) months, respectively. The CBR was 29% (95% CI 13% to 44%). they observed3 (8%) partial responses (PRs), 2 (6%) minor responses (<30% tumor shrinkage) and 12 (34%) stable diseases (SDs).For six patients (17%), PR/SD lasted 6 months. |
| Disease Control Rate: | 0.48 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4 (95% CI 2-5) months |
| Median OS A vs. C: | 7 (95% CI 7-8) months |
| Adverse Event(agent arm): | In general, drugrelated adverse events were limited to grade 1 or 2. they noted the following grade 3 and 4 toxic effects: anemia 2 (6%), thrombocytopenia 2 (6%), nausea 1 (3%), asymptomatic lipase G4 increase 1 (3%), abdominal cramps 1 (3%), oral mucositis 1 (3%), hand-foot skin reaction 3 (9%) and 1 (3%) skin metastasis bleeding (after a minor trauma). |
| Conclusions: | Sorafenib demonstrated activity as a second or thirdline treatment in terms of PFS at 4 months with some unprecedented longlasting responses. Sorafenib, the first targeted therapy showing activity in osteosarcoma patients, deserves further investigations. |