NCT05012371

Lenvatinib With Everolimus Versus Cabozantinib for Second-Line or Third-Line Treatment of Metastatic Renal Cell Cancer

A Phase II Study of Lenvatinib Plus Everolimus Versus Cabozantinib in Patients With Metastatic Renal Cell Carcinoma That Progressed on A PD-1/PD-L1 Checkpoint Inhibitor

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial compares the effects of lenvatinib given in combination with everolimus to the effects of cabozantinib given alone in treating patients with renal cell cancer (RCC) that has spread to other parts of the body (metastatic) and that got worse on a previous PD-1/PD-L1 checkpoint inhibitor. Lenvatinib, everolimus, and cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed description

PRIMARY OBJECTIVE: I. To compare the efficacy of lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. SECONDARY OBJECTIVES: I. To compare tumor responses to lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. II. To compare health-related quality of life (HRQoL) and safety of lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. III. To compare overall survival (OS) with lenvatinib plus everolimus versus cabozantinib in patients with mRCC who developed progressive disease after 1-2 lines of therapy, including a PD-1/PD-L1 checkpoint inhibitor. EXPLORATORY OBJECTIVE: I. To assess whether alterations to c-MET, VEGF, mTOR, and FGFR are associated with response to therapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM A: Patients receive lenvatinib orally (PO) once daily (QD) and everolimus PO QD. Cycles repeat every 30 days in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive cabozantinib PO QD. Cycles repeat every 30 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months.

Conditions

• Advanced Clear Cell Renal Cell Carcinoma
• Metastatic Clear Cell Renal Cell Carcinoma
• Stage III Renal Cell Cancer AJCC v8
• Stage IV Renal Cell Cancer AJCC v8

Interventions

Type	Name	Description
DRUG	Cabozantinib	Given PO
DRUG	Everolimus	Given PO
DRUG	Lenvatinib	Given PO
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2022-02-16
• Primary completion: 2027-10-25
• Completion: 2027-10-25
• First posted: 2021-08-19
• Last updated: 2026-03-05

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study