Entry Detail
| General information | |
| Database: | DB01043 |
| Objective: | a phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc human epidermal growth factor receptor 2Negative breast CancEr (the RESILIENCE study) |
| Authors: | Jos¨¦ Baselga |
| Title: | a phase 3 tRial comparing capecitabine in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc human epidermal growth factor receptor 2Negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial. |
| Journal: | Trials |
| Year: | 2013 |
| PMID: | 23876062 |
| Trial Design | |
| Clinical Trial Id: | NCT01234337 |
| Agent: | sorafenib |
| Target: | Vascular endothelial growth factor receptor 1 BRaf protooncogene serine/threonineprotein kinase Protooncogene tyrosineprotein kinase receptor ret |
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | capecitabine + SorafenIb |
| Study Type: | a multinational, randomized, doubleblind, placebocontrolled, phase III trial designed to assess the efficacy and safety of sorafenib in combination with capecitabine in patients with locally advanced or metastatic human epidermal growth factor receptor IInegative breast cancer who received previous treatment with a taxane and anthracycline. |
| Key Patients Feature: | more than and equal to 18 years of age, less than and equal to 1 prior chemotherapy regimen for metastatic disease, and resistant to/failed taxane and anthracycline or no indication for further anthracycline. Prior treatment with a vascular endothelial growth factor inhibitor is not allowed. Patients with significant cardiovascular disease or active brain metastases are not eligible. |
| Biomarker: | PIK3CA, BRAF, and KRAS |
| Biomark Analysis: | NA |
| Control Group Info: | capecitabine plus placebo |
| Treatment Info: | capecitabine (1000 mg/m2 orally twice daily (BID), days 1 to 14 of 21) in combination with sorafenib (orally BID, days 1 to 21, total dose 600 mg/day) or matching placebo. Capecitabine and sorafenib/placebo doses can be escalated to 1250 mg/m2 BID and 400 mg BID, respectively, as tolerated, or reduced to manage toxicity. Dose reescalation after a reduction is allowed for sorafenib/placebo but not for capecitabine. |
| Primary End Point: | PFS by blinded independent central review (Response Evaluation Criteria in Solid Tumors 1.1 criteria). |
| Secondary End Point: | overall survival, time to progression, overall response rate, duration of response, and safety. |
| Patients Number: | 519 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | 13.5% (9.7 to 18.2) vs 15.5% (11.4 to 20.4) |
| Disease Control Rate: | 60.5%(54.4 to 66.4) vs 58.3% (52.2 to 64.2) |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 166days (131 to 206) vs 165days (126 to 204) (HR= 0.973; 95%CI: 0.779 1.217; P=0.405618) |
| Median OS A vs. C: | 575days (467 to 645) vs 616 days (546 to 687) (HR= 1.195; 95%CI: 0.9431.513; P=0.930088) |
| Adverse Event(agent arm): | Anaemia; Febrile neutropenia; Pericardial effusion ; Aplasia; Abdominal pain |
| Conclusions: | The RESILIENCE study is an essential step for the development of sorafenib in MBC, as it will provide definitive PFS data and more definitive OS data and inform on the management of HFSRHFS. An effective alloral combination regimen for human epidermal growth factor receptor 2negative disease would be an important addition to the therapeutic armamentarium in this patient population. |