Overview

This trial is active, not recruiting.

Condition metastatic renal cell carcinoma
Treatments lenvatinib, everolimus
Phase phase 1/phase 2
Targets mTOR, VEGF, FKBP-12
Sponsor Eisai Inc.
Start date August 2010
End date June 2014
Trial size 153 participants
Trial identifier NCT01136733, E7080-G000-205

Summary

This is an open-label, multicenter, Phase 1b/2 study of lenvatinib alone and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted treatment.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
lenvatinib E7080
taken orally,once a day
(Experimental)
lenvatinib E7080
taken orally,once a day
everolimus
orally once a day
(Active Comparator)
everolimus
orally once a day

Primary Outcomes

Measure
Phase 1b=Dose-limiting toxicity (DLT)
time frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1 and 15)
Phase 1b= Maximally tolerated dose (MTD)
time frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1 and 15)
Phase 1b= Recommended Phase 2 (RP2) dose
time frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1 and 15)
Phase 2=Progression-free survival (PFS)
time frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1 and 15)

Secondary Outcomes

Measure
Progression-Free Survival (PFS)
time frame: Time is from Baseline to first evidence of disease progression.Assessments are performed every 2 months
Overall Survival (OS)
time frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months
Objective Response Rate (ORR)
time frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months
Disease Control Rate (DCR)
time frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months
Durable Stable Disease (SD)
time frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months
Clinical Benefit Rate (CBR)
time frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months
Pharmacokinetic (PK) and pharmacodynamic (PD) profile.
time frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months

Eligibility Criteria

Male or female participants from 18 years up to 99 years old.

Select Inclusion Criteria: - Histologically confirmed diagnosis of renal cell carcinoma. - Phase 2: Histological or cytological confirmation of predominant clear cell RCC (original tissue diagnosis of RCC is acceptable). - Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1). - Phase 2: One prior vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/tivozanib) for unresectable advanced or metastatic RCC. - Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. - Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit. Select Exclusion Criteria: Phase 1b or Phase 2 specific per below: - Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (CNS) are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only. Phase 2 only: Subjects with CNS (e.g., brain or leptomeningeal) metastasis are excluded. - Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC. Phase 1b or Phase 2 specific per below: - Phase 1b only: Prior exposure to lenvatinib. Phase 2 only: Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor. - Subjects should not have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment. Major surgery within 3 weeks prior to the first dose of study drug. - Subjects having greater than 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria. - Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose at 1.5 x ULN. - Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months. - Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients. - Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.

Additional Information

Official title An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Eisai Inc..