| General information |
| Database: | DB00488 |
| Objective: | To evaluate the feasibility and efficacy of sorafenib and everolimus in renal cell carcinoma (RCC). |
| Authors: | Hainsworth JD, et al |
| Title: | Sorafenib and everolimus in advanced clear cell renal carcinoma: a phase I/II trial of the SCRI Oncology Research Consortium. |
| Journal: | Cancer Invest. |
| Year: | 2013 |
| PMID: | 23614653 |
| Trial Design |
| Clinical Trial Id: | NCT00392821 |
| Agent: | sorafenib and everolimus
|
| Target: | NA
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | sorafenib+ everolimus |
| Study Type: | multicenter, communitybasedphase I/II trial |
| Key Patients Feature: | Eligible patients were required to have metastatic or unresectable locally recurrent renal cell carcinoma in whichat least 75% of the cancer had clear cell histology. Previously untreated patients were eligible; in addition, treatmentwith one regimen containing immunotherapy (interferon, interleukin2), chemotherapy, or a combination was allowed.Patients could also have received up to one previous antiangiogenesis agent; however, patients were not allowed tohave received previous sorafenib or any previous mTOR inhibitor. Nephrectomy was required except where clinicallycontraindicated. Additional entry criteria included ECOGperformance status 0 or 1, measurable disease (RECIST), adequate blood counts (neutrophils more than and equal to 1, 500/¦ÌL, plateletsmore than and equal to 75, 000/¦ÌL, hemoglobin more than and equal to 9 g/dL), bilirubin less than and equal to 1.5 mg/dLand AST/ALT less than and equal to 2.5 times the institutional upper limits ofnormal (ULN) or < 5 times ULN with documented livermetastases, and serum creatinine less than and equal to 2 mg/dL. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Phase I: Two dose levels were evaluated during the phase I portion of this trial. The initial dose level included sorafenib400 mg BID and everolimus 35 mg once weekly, both given orally.phase II: All patients in the phase II portion of the trial received sorafenib 200 mg PO BID and everolimus 35 mg PO once weekly. |
| Primary End Point: | progression free survival |
| Secondary End Point: | objective response rate and overall survival. |
| Patients Number: | 76 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Nine patients (16%) without previous antiangiogenic therapy had objective responses, as compared with 1 patient (5%) with previous exposure to targeted agents. Thirtyseven previously untreated patients (67%) had measurable decrease in tumor measurements, as compared with 6 patients (30%) who had received previous antiangiogenic therapy |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.45 months (95% CI: 3.8-7.6) |
| Median OS A vs. C: | 19.1 months (95% CI: 11.4-22.4 months) |
| Adverse Event(agent arm): | Skin toxicity, fatigue, hypertension, proteinuria, and mucositis (usually Grade 2) were common. |
| Conclusions: | ifty percent doses of sorafenib and everolimus they were required when these drugs they were combined. No increase in efficacy was suggested; toxicity was modestly increased. |