A 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

NCT02915783 | Completed Phase 2 Results FDA Drug

• 1 other identifier: E7080-M001-221
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 8

Brief Summary

This is a single-arm, multicenter, Phase 2 study of lenvatinib in combination with everolimus in participants with unresectable advanced or metastatic non clear cell renal cell carcinoma (nccRCC) who have not received any chemotherapy for advanced disease. The primary objective of the study is to evaluate the objective response rate (ORR). This study consists of three phases: a Pretreatment Phase (Screening and Baseline Periods), a Treatment Phase (starting Cycle 1, Day 1), and a Posttreatment Phase (End of Treatment Visit and survival Follow-up).

Conditions

Non Clear Cell Renal Cell Carcinoma (nccRCC)

Keywords

unresectable advanced; metastatic

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR was assessed by the investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. ORR was defined as the percentage of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (\<) 10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From the date of the first dose of study drug to the date of the first documentation of disease progression or death, whichever occurred first (up to approximately 3 years 9 months)

Secondary Outcomes (2)

• Progression-free Survival (PFS)

  From the date of the first dose of study drug to the date of the first documentation of disease progression or death, whichever occurred first (up to approximately 3 years 9 months)

• Overall Survival (OS)

  From the date of the first dose of study drug until the date of death from any cause (up to approximately 4 years 8 months)

Study Arms (1)

lenvatinib 18 mg/day and everolimus 5 mg/day

EXPERIMENTAL

Participants will receive initial doses of lenvatinib 18 milligrams per day (mg/day) (one 10-mg capsule and two 4-mg capsules) and everolimus 5 mg/day (5-mg tablets). Capsules and tablets are to be taken orally in immediate succession once a day (QD), and dosing is recommended to occur at approximately the same time each morning (consistently either with or without food).

Drug: lenvatinib; Drug: everolimus

Interventions

lenvatinib DRUG

4 mg and 10 mg capsules

lenvatinib 18 mg/day and everolimus 5 mg/day

everolimus DRUG

5 mg tablets

lenvatinib 18 mg/day and everolimus 5 mg/day

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 following criteria:
• At least 1 lesion of ≥10 millimeters (mm) in the longest diameter for a nonlymph node or ≥15 mm in the short axis diameter for a lymph node that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computerized tomography (CT) or magnetic resonance imaging (MRI);
• Lesions that have had external beam radiotherapy (EBRT) or locoregional therapies such as radiofrequency (RF) ablation must show evidence of subsequent progressive disease (substantial size increase of ≥20%) to be deemed a target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Blood pressure (BP) ≤140/90 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 function as evidenced by calculated creatinine clearance ≥30 milliliters (mL)/minute according to the Cockcroft and Gault formula
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥1.5 × 10\^9/liter (L);
• Hemoglobin ≥10.0 grams per deciliter (g/dL) (can be corrected by growth factor or transfusion prior to first dose of study drug);
• Platelet count ≥100 × 10\^9/L
• Adequate liver function:
• Bilirubin ≤1.5 × upper limit of normal (ULN) except for unconjugated hyperbilirubinemia or Gilbert's syndrome;
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if participant has liver metastases). If ALP is \>3 × ULN (in the absence of liver metastases) or \>5 × ULN (in the presence of liver metastases) AND participants are also known to have bone metastases, the liver-specific ALP must be separated from the total and used to assess the liver function instead of the total ALP.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02214, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Texas Oncology

Dallas, Texas, 75254, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Related Publications (1)

• Hutson TE, Michaelson MD, Kuzel TM, Agarwal N, Molina AM, Hsieh JJ, Vaishampayan UN, Xie R, Bapat U, Ye W, Jain RK, Fishman MN. A Single-arm, Multicenter, Phase 2 Study of Lenvatinib Plus Everolimus in Patients with Advanced Non-Clear Cell Renal Cell Carcinoma. Eur Urol. 2021 Aug;80(2):162-170. doi: 10.1016/j.eururo.2021.03.015. Epub 2021 Apr 16.

  PMID: 33867192 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

lenvatinib; Everolimus

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_oncmedinfo@eisai.com

1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2016
• First Posted: September 27, 2016
• Study Start: February 20, 2017
• Primary Completion: November 2, 2021
• Study Completion: November 2, 2021
• Last Updated: January 17, 2023
• Results First Posted: July 13, 2020

Record last verified: 2021-06

Locations

US (8)