| General information |
| Database: | DB00473 |
| Objective: | Everolimus (mammalian target of rapmaycin (mTOR) inhibitor) and dovitinib (vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) inhibitor) demonstrate activity in metastatic clear cell renal cancer. The combination of these agents has a broad spectrum of relevant activity. The combination is explored in thisphase Ib study. |
| Authors: | Powles T, et al |
| Title: | a phase Ib study investigating the combination of everolimus and dovitinib in vascular endothelial growth factor refractory clear cell renal cancer. |
| Journal: | Eur J Cancer. |
| Year: | 2014 |
| PMID: | 24908540 |
| Trial Design |
| Clinical Trial Id: | NCT01714765 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | clear cell renal carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | everolimus + dovitinib |
| Study Type: | phase Ib study |
| Key Patients Feature: | Patients with metastatic clear cell RCC were eligiblefor this study. patients were required to have had progressive disease while taking VEGF targeted therapyand enrolled within 6 months of failing previous targeted therapy (VEGF or mTOR therapy). patients wererequired to have a performance status of 0 or 1, over3 months life expectancy, no evidence of cardiac diseasewithin the last 6 months, adequate organ function(bilirubin 6 1.5 upper limit of normal (ULN), transaminases 6 3 ULN, creatinine 6 2 ULN, absoluteneutrophil countP 1.5 109/L, plateletsP 100 109/L)and no contraindications for dovitinib or everolimus. |
| Biomarker: | Sequential fluorodeoxyglucose positron emission tomography (FDGPET) was used as a surrogate marker of response |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Up to four cohorts of three to six patients (3+3 design) were treated with escalating doses of everolimus and dovitinib. |
| Primary End Point: | the maximum tolerated dose for the combination of dovitinib and everolimus. |
| Secondary End Point: | the occurrence of other toxicity. |
| Patients Number: | 18 |
| Trial Results |
| DLT_MTD: | Fifteen patients received the MTD, which was everolimus 5mg orally (PO) once daily (OD) and dovitinib 200mg PO day 15/7. The MTD was associated with toxicity, which included fatigue, mucositis and diarrhoea in 73%, 53% and 53% (Common Toxicity Criteria (CTC) grade 14) of patients, respectively. Frequent biochemical abnormalities occurred (such as hypertriglyceridaemia in 67%). |
| Objective Response Rate: | The response rate at the MDT was 1/15 (7%) while the progression free survival for the MTD was 7 months (95% confidence interval (CI) 2.211 months). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 7.0 months (95% CI 2.3- 10 months). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The MTD was associated with toxicity, which included fatigue, mucositis and diarrhoea in 73%, 53% and 53% (Common Toxicity Criteria (CTC) grade 1-4) of patients, respectively. |
| Conclusions: | Dovitinib and everolimus had modest activity, but did not meet all of the planned efficacy endpoints. Fatigue was the dose limiting toxicity. |