Clinical Trial 18878

Cancer Type: Genitourinary
Interventions:E7080 (Lenvatinib); Lenvatinib (Lenvima); everolimus (RAD001)

Study Type: Treatment
Phase of Study: Phase II
Investigators:

  • Mayer Fishman

Overview

Study Title

A Single-Arm, Multicenter, Phase 2 Trial to Evaluate Efficacy and Safety of Lenvatinib in Combination with Everolimus in Subjects with Unresectable Advanced or Metastatic Non Clear Cell Renal Cell Carcinoma (nccRCC) Who Have Not Received any Chemotherapy for Advanced Disease

Summary

The purpose of the study is to evaluate the effectiveness (how well they work) and the safety of the study drugs, the combination of lenvatinib and everolimus, in participants with unresectable (not able to be removed by surgery) advanced or metastatic (spread from one organ to another) non clear cell renal carcinoma (nccRCC) (a specific type of kidney cancer) who have not received any chemotherapy for advanced disease.

Objective

Primary Objective: - To evaluate objective response rate (ORR) of lenvatinib in combination with everolimus in subjects with unresectable advanced or metastatic non clear cell renal cell carcinoma(nccRCC) who have not received any chemotherapy for advanced disease. Secondary Objectives: - To assess safety and tolerability of lenvatinib in combination with everolimus. - To evaluate progression-free survival (PFS). - To evaluate overall survival (OS). - To assess the pharmacokinetic (PK) profiles of lenvatinib and everolimus during combination therapy in subjects with nccRCC. Exploratory Objectives: - To explore clinical benefit rate (CBR). - To explore disease control rate (DCR). - To explore duration of response (DOR). - To identify and explore tumor and blood biomarkers that correlate with clinical outcomes, including efficacy. - To explore the relationship of population PK derived exposure parameters to biomarker, safety, and efficacy data using a model-based approach.

Inclusion Criteria

  • Males or females age ≥18 years at the time of informed consent form (ICF).
  • Participants with histologically confirmed non clear cell renal cell carcinoma (nccRCC) who have not received any chemotherapy for advanced disease. Participants must have one of the following subtypes of nccRCC: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
  • Radiologically measurable disease meeting the study criteria.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
  • Blood pressure (BP) less than or equal to140/90 millimeters of mercury (mmHg) at Screening with or without antihypertensive medications and no change in antihypertensive medications within 1 week prior to Cycle 1/Day 1.
  • Adequate renal, liver and bone marrow function.
  • Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.

  • Exclusion Criteria

  • Predominant clear cell renal cell carcinoma (RCC).
  • Prior anticancer chemotherapy or targeted therapy for advanced nccRCC.
  • Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor.
  • Known intolerance to lenvatinib, everolimus (or other rapamycin derivatives), or any of the excipients.
  • Major surgery performed within 3 weeks prior to the first dose of study drugs or scheduled for major surgery during the study.
  • Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib or everolimus.
  • Participants having >1+ proteinuria on urine dipstick testing will undergo 24 hour urine collection for quantitative assessment of proteinuria. Participants with urine protein ≥1 grams (g)/24 hours will be ineligible.
  • Fasting total cholesterol ˃300 milligrams (mg)/dL (or ˃7.75 millimoles [mmol]/L) or fasting triglycerides level ˃2.5 × ULN. Note: these participants can be included after initiation or adjustment of lipid-lowering medication.
  • Uncontrolled diabetes as defined by fasting glucose >1.5 times the ULN. Note: In case this threshold is exceeded, these participants can only be included after initiation or adjustment of glucose-lowering medication.
  • Known history of, or any evidence of, interstitial lung disease or active noninfectious pneumonitis.
  • Significant cardiovascular impairment: history of (a) congestive heart failure greater than New York Heart Association (NYHA) Class II; (b) unstable angina; (c) myocardial infarction; (d) stroke; or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs.
  • Prolongation of QTcF interval to >480 milliseconds (msec).
  • Known history of human immunodeficiency virus (HIV) positive.
  • Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] RNA detected).
  • Clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug.
  • Participants with central nervous system (CNS) (e.g., brain or leptomeningeal) metastases.
  • Other active malignancy (except definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or bladder) within the past 24 months.
  • Females who are breastfeeding or pregnant at Screening or Baseline.
  • Females of childbearing potential who: Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception according to study guidelines throughout the entire study period and for 28 days after study drug discontinuation
  • Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above.
  • Evidence of clinically significant disease (e.g., cardiovascular, respiratory, gastrointestinal, renal, or infectious disease) that in the opinion of the investigator(s) could affect the participant's safety or interfere with the study assessments.
  • Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in a clinical study.
  • Active and current use of illegal recreational drugs.
  • Currently enrolled in another interventional clinical study or used any investigational drug or device within the past 28 days preceding informed consent.