Entry Detail
| General information | |
| Database: | DB00579 |
| Objective: | Chondrosarcoma (CS) is a rare and heterogeneous sarcoma in which, after failure of surgery and radiotherapy, chemotherapy plays only a marginal role. Different molecular pathways have been shown to be activated in CS; in particular, both isoforms of plateletderived growth factor receptor (PDGFR) are expressed and phosphorylated. These observations prompted investigation of the activity of imatinib mesylate (IM) in patients with advanced CS in a phase 2 trial. |
| Authors: | Grignani G, et al |
| Title: | a phase 2 trial of imatinib mesylate in patients with recurrent nonresectable chondrosarcomas expressing plateletderived growth factor receptor¦Á or ¦Â: An Italian Sarcoma Group study. |
| Journal: | cancer |
| Year: | 2011 |
| PMID: | 20925044 |
| Trial Design | |
| Clinical Trial Id: | EUDRACT number 200600644633 |
| Agent: | imatinib mesylate |
| Target: | Abl Plateletderived growth factor receptor Mast/stem cell growth factor receptor |
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | Chondrosarcomas |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a nonrandomized, multicenter, openlabelphase II trial |
| Key Patients Feature: | The current study was a nonrandomized, multicenter, openlabelphase 2 trial in patients with histologically proven CS with nonresectable or metastatic disease. In allpatients, the histological diagnosis was centrally revietheydand PDGFR expression was confirmed by immunohistochemical staining metastatic and/or nonresectable CS were enrolled at 6 centers. All patients had received at least 1 priorline of chemotherapy |
| Biomarker: | immunohistochemical expression of either PDGFR¦Á or PDGFR¦Â |
| Biomark Analysis: | failed to demonstrate meaningful clinical activity |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with 400 mg of IM administered twice daily until disease progression or unacceptable toxicity. |
| Primary End Point: | objective response |
| Secondary End Point: | progression free survival (PFS) at 4 months, overall survival, and clinical benefit. |
| Patients Number: | 26 |
| Trial Results | |
| DLT_MTD: | Edema was the most commongrade 3 to 4 toxicity, and was noted in 3 (12%)patients, follotheyd by skin rash in 2 (8%) patients, leukopeniain 2 (8%) patients, and muscle cramps in 1 (4%)patient. |
| Objective Response Rate: | No objective response was demonstrated. The 4month PFS rate was 31% (95% confidenceinterval [95% CI], 16%53%). The median overall survival was 11 months (95% CI, 6 months15 months). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3 months (95% CI, 2.2 months7.7 months) |
| Median OS A vs. C: | 11 months (95% CI, 6 months15 months). |
| Adverse Event(agent arm): | Adverse events were observed in 18 (69%) patients, and dose reductions were required in 15 (58%) patients. they did not observe any drugrelated deaths. Edema was the most common grade 3 to 4 toxicity, and was noted in 3 (12%) patients, follotheyd by skin rash in 2 (8%) patients, leukopenia in 2 (8%) patients, and muscle cramps in 1 (4%) patient. As expected, the observed side effects were reversible either with dose reductions or short drug interruptions. |
| Conclusions: | IM was found to be relatively welltolerated, but failed to demonstrate meaningful clinical activity in terms of both objective response and freedom from disease progression. Advanced CS remains an incurable disease, and effective targeted therapies are still awaited. |