Study of Lenvatinib in Combination With Everolimus in Participants With Unresectable Advanced or Metastatic Renal Cell Carcinoma (RCC)

NCT02454478 | Completed Phase 1 Results

• 1 other identifier: E7080-J081-112
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief Summary

Phase 1 study to investigate the tolerability and safety of lenvatinib in combination with Everolimus in participants with unresectable advanced or metastatic RCC.

Conditions

Carcinoma, Renal Cell

Keywords

lenvatinib; Everolimus; Carcinoma; Unresectable advanced renal cell carcinoma; Metastatic renal cell carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Any Dose Limiting Toxicity (DLT)

  DLT was defined as toxicity related to the combination therapy and was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).

  From first dose of study drug up to Cycle 1 Day 28 (Cycle length=28 days)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Baseline up to 30 days after the last dose of study drug (up to approximately 21.5 months)

Secondary Outcomes (9)

• Cmax: Maximum Observed Plasma Concentration for Levatinib and Everolimus

  Cycle 1 Day 1 predose and at 1, 2, 4 ,8, and 24 hours postdose (Cycle length=28 days)

• Css,Max: Maximum Observed Plasma Concentration at Steady State for Levatinib and Everolimus

  Cycle 1 Day 15 predose and at 1, 2, 4 ,8, and 24 hours postdose (Cycle length=28 days)

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Levatinib and Everolimus

  Cycle 1 Day 1 predose and at 1, 2, 4 ,8, and 24 hours postdose (Cycle length=28 days)

• Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State for Levatinib and Everolimus

  Cycle 1 Day 15 predose and at 1, 2, 4 ,8, and 24 hours postdose (Cycle length=28 days)

• AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Levatinib and Everolimus

  Cycle 1 Day 1 and Cycle 1 Day 15 predose and at 1, 2, 4 ,8, and 24 hours postdose (Cycle length=28 days)

Study Arms (1)

Lenvatinib plus Everolimus

EXPERIMENTAL

Drug: Lenvatinib; Drug: Everolimus

Interventions

Lenvatinib DRUG

Lenvatinib plus Everolimus

Everolimus DRUG

Also known as: Lenvatinib plus Everolimus orally once a day

Lenvatinib plus Everolimus

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary agreement to provide written informed consent of this study.
• Willing and able to comply with all aspects of the protocol after being fully informed of the content.
• Males or females aged greater than or equal to 20 years at the time of informed consent.
• Histological or cytological confirmation of RCC.
• Participants must have confirmed diagnosis of unresectable advanced and/or metastatic RCC.
• Disease progression following vascular endothelial growth factor (VEGF) targeted therapy.
• Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0 to 1.
• Adequately controlled blood pressure with or without the use of antihypertensive agents.
• Participants with adequate function of major organs.
• Adequate blood coagulation function, defined as international normalized ratio (INR) less than or equal to 1.5.
• Survival expectation of 3 months or longer after study enrollment.
• Participants with adequate washout period from the end of prior treatment to the start of study drug administration.
• Females of childbearing potential must not have had unprotected sexual intercourse within 28 days before participant registration and must agree to use a highly effective method of contraception throughout the entire study period and for 30 days after final administration of investigational drug. If currently abstinent, the participant must agree to use a double-barrier method as described above if she becomes sexually active during this study period or for 30 days after investigational drug discontinuation. Females who are using hormonal contraceptives must have been on a stable dose of the same hormonal contraceptive product for at least 4 weeks before administration and must continue to use the same contraceptive during this study and for 30 days after investigational drug discontinuation.
• Male participants and their female partners must meet the criteria above.

You may not qualify if:

• Participants with central nervous system (CNS) metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
• Prior exposure to lenvatinib.
• Participants who have not recovered from toxicities to less than or equal to Grade 1 as a result of prior anticancer therapy, except alopecia.
• Major surgery within 3 weeks prior to the first dose of lenvatinib.
• Participants with a urine protein greater than or equal to 1 gram per 24 hours (g/24 hours).
• Uncontrollable diabetes as defined by fasting glucose greater than 1.5\* upper limit of normal (ULN).
• Fasting total cholesterol greater than 7.75 millimole per liter (mmol/L) (greater than 300 milligram per decilitre \[mg/dL\]).
• Fasting triglycerides greater than 2.5 \* ULN.
• Any condition that might affect the absorption of lenvatinib and/or everolimus.
• Significant cardiovascular impairment.
• Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic INR monitoring.
• Active hemoptysis.
• Active infections that require systemic treatment.
• Human immunodeficiency virus (HIV) positive.
• Hepatitis B virus (HBV).

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (3)

Eisai Trial Site #1

Chiba, Japan

Location

Eisai Trial Site #1

Tokyo, Japan

Location

Eisai Trial Site #2

Tokyo, Japan

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Carcinoma

Interventions

lenvatinib; Everolimus

Condition Hierarchy (Ancestors)

Adenocarcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2015
• First Posted: May 27, 2015
• Study Start: July 1, 2015
• Primary Completion: May 29, 2017
• Study Completion: May 29, 2017
• Last Updated: March 19, 2019
• Results First Posted: February 8, 2019

Record last verified: 2018-09

Locations

JP (3)