| General information |
| Database: | DB00574 |
| Objective: | They aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable highgrade osteosarcoma progressing after standard treatment. |
| Authors: | Grignani G, et al |
| Title: | Sorafenib and everolimus for patients with unresectable highgrade osteosarcoma progressing after standard treatment: a nonrandomisedphase 2 clinical trial. |
| Journal: | Lancet Oncol. |
| Year: | 2015 |
| PMID: | 25498219 |
| Trial Design |
| Clinical Trial Id: | NCT01804374 |
| Agent: | sorafenib everolimus
|
| Target: | NA
|
| Cancer Type: | soft tissue sarcomas |
| Cancer Subtype: | osteosarcoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | sorafenib+everolimus |
| Study Type: | a nonrandomisedphase II clinical trial |
| Key Patients Feature: | 1. Patients with histologically documented and not surgically resectable* or metastatic highgrade osteosarcomawhich progressed after first or second line treatments for relapsing disease.2. Measurable disease as defined by having at least one unidimensional (RECIST v1.1 / bone lesions areallowed) measurable lesion that can be accurately measured by means of CT or MRI. Baseline evaluationsmust be completed within 28 days prior to enrollment.3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0/ 1 and an estimated life expectancy ofat least 3 months. Patients with and ECOG PS 2 are eligible if the PS 2 depends solely on orthopedic problems.4. Estimated life expectancy of at least 3 months.5. Age more than and equal to 18 years.6. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to beconducted within 7 days prior to start of treatment: Hemoglobin > 9.0 g/dl Absolute neutrophil count (ANC) >1, 500/mm3 Platelet count more than and equal to 100, 000/¦Ìl Total bilirubin < 1.5 times the upper limit of normal ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liverinvolvement of their cancer) PTINR/PTT < 1.5 x upper limit of normal (Patients who are being therapeutically anticoagulated with anagent such as warfarin or heparin will be allowed to participate provided that no prior evidence ofunderlying abnormality in these parameters exists) Serum creatinine < 2 x upper limit of normal.7. Written informed consent.Eligibility criteria to lung metastasectomy: no uncontrollable extrapulmonary disease; metastatic lung disease has to be amenable to complete resection leaving the patient with adequate lungfunction for an acceptable quality of life; no mediastinal or chest wall involvement unless it is the unique metastatic site; absence of pericardial or pleural effusions; acceptable overall operative risk. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. |
| Primary End Point: | 6 month progression free survival (PFS) |
| Secondary End Point: | NA |
| Patients Number: | 38 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5 months (95% CI 2-7) with eight (21%) of 38 patients receiving sorafenib and everolimus for 8 months or more. |
| Median OS A vs. C: | 11 months (95% CI 8-15) with 14 (37%) of 38 patients alive after 12 months and two (5%) alive after 24 months |
| Adverse Event(agent arm): | The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required transthoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatmentrelated deaths. |
| Conclusions: | Although the combination of sorafenib and everolimus showed activity as a furtherline treatment for patients with advanced or unresectable osteosarcoma, it did not attain the prespecified target of 6 month PFS of 50% or greater. |