Entry Detail
| General information | |
| Database: | DB00481 |
| Objective: | Lenvatinib is an oral multitargeted tyrosine kinase inhibitor of VEGFR13, FGFR14, PDGFR¦Â, RET, and KIT. Everolimus is an oral mammalian target of rapamycin inhibitor approved for advanced renal cell carcinoma (RCC). Thisphase 1b study assessed safety, maximum tolerated dose (MTD), and preliminary antitumor activity of lenvatinib plus everolimus in metastatic RCC (mRCC) patients. |
| Authors: | Molina AM, et al |
| Title: | a phase 1b clinical trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in combination with everolimus for treatment of metastatic renal cell carcinoma (RCC). |
| Journal: | Cancer Chemother Pharmacol |
| Year: | 2014 |
| PMID: | 24190702 |
| Trial Design | |
| Clinical Trial Id: | NCT01136733 |
| Agent: | lenvatinib |
| Target: | Alpha plateletderived growth factor receptor Mast/stem cell growth factor receptor Protooncogene tyrosineprotein kinase receptor ret VEGF receptor Fibroblast growth factor receptor |
| Cancer Type: | renal cell carcinoma |
| Cancer Subtype: | advanced renal cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | lenvatinib (E7080) + everolimus |
| Study Type: | phase Ib component of a multicenter, openlabel, phase Ib/II study. |
| Key Patients Feature: | patients were aged more than and equal to 18 years, with histologically confirmed and documented evidence of unresectable advancedor mrCC and disease progression after prior therapy targeting the VegF domain. two patients who had receivedno prior regimens were enrolled prior to a protocolamendment. eligible patients had an eastern CooperativeOncology group performance status of 0 or 1, adequately ontrolled blood pressure, adequate hematologic, hepatic, renal, and blood coagulation function, and internationalizednormalized ratio (Inr) of less than and equal to 1.5. there was no upper limiton prior therapies. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Starting dose was lenvatinib 12 mg once daily with everolimus 5 mg once daily administered continuously in 28day cycles using a conventional 3 + 3 doseescalation design. |
| Primary End Point: | the doselimiting toxicities (Dlts), maximum tolerated dose (MtD),and recommended phase 2 dose |
| Secondary End Point: | NA |
| Patients Number: | 20 |
| Trial Results | |
| DLT_MTD: | MTD was established as once daily lenvatinib 18 mg plus everolimus 5 mg.The most common treatmentrelated treatmentemergent adverse events (all dosing cohorts) were fatigue 60 % (Grade more than and equal to 3: 10 %), mucosal inflammation 50 %, proteinuria (Grade more than and equal to 3: 15 %), diarrhea (Grade more than and equal to 3: 10 %), vomiting (Grade more than and equal to 3: 5 %), hypertension, and nausea, each 40 %. |
| Objective Response Rate: | In MTD and lotheystdose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33 %) and 9 (50 %) patients, respectively. |
| Disease Control Rate: | 80% in all patients. 85.7% in cohort 1; 81.8% in cohort 2; 50% in cohort 3. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | the median progression free survival (PFS) was 330 days (95 % CI 157-446; approximately 10.9 months) at the MtD and lotheyrdose cohort, while the 6 and 12month PFS rates were 72.1 % (95 % CI 48.8- 95.4 %) and 49.5 % (95 % CI 22.7-76.2 %), respectively. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | the most common treatmentrelated treatmentemergent adverse events (all dosing cohorts) were fatigue 60 % (grade more than and equal to 3: 10 %), mucosal inflammation 50 %, proteinuria (grade more than and equal to 3: 15 %), diarrhea (grade more than and equal to 3: 10 %), vomiting (grade more than and equal to 3: 5 %), hypertension, and nausea, each 40 %. In MtD and lotheystdose cohorts (n = 18), best responses of partial response and stable disease were achieved in 6 (33%) and 9 (50 %) patients, respectively. |
| Conclusions: | Lenvatinib 18 mg combined with everolimus 5 mg was associated with manageable toxicity consistent with individual agents and no new safety signals. Observed activity warrants further evaluation of the combination in advanced RCC patients. |