Lenvatinib + Everolimus for Kidney Cancer

Overseen By Yousef Zakharia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Yousef Zakharia

Disqualifiers: Other cancers, CNS metastases, Hypertension, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, lenvatinib and everolimus, to determine if they can shrink kidney cancer tumors, making surgical removal easier. It focuses on patients with advanced kidney cancer that has spread to nearby areas or other parts of the body. Suitable candidates for this trial have been diagnosed with locally advanced or metastatic kidney cancer that could potentially be treated with surgery. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining lenvatinib and everolimus has raised safety concerns in past studies. One study found that 54.9% of patients needed to lower their lenvatinib dose due to side effects, and 25.6% had to pause treatment temporarily. Everolimus also presented issues, with 17.1% of patients needing a dose adjustment. These findings suggest that while the treatment can be effective, side effects may necessitate changes in administration. Participants should consider these potential issues when deciding to join a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Lenvatinib and Everolimus for kidney cancer because these drugs work differently than the standard treatments. Lenvatinib targets multiple pathways involved in tumor growth, including the VEGF receptor, which is key in the formation of blood vessels that supply the tumor. Everolimus, on the other hand, inhibits mTOR, a protein that helps cancer cells grow and survive. This dual approach is promising because it can potentially cut off both the blood supply to the tumor and the internal signals that promote cancer cell survival, offering a more comprehensive attack on the cancer than traditional therapies.

What evidence suggests that the combination of lenvatinib and everolimus could be effective for kidney cancer?

In this trial, participants will receive a combination of lenvatinib and everolimus before undergoing cytoreductive nephrectomy. Research has shown that using lenvatinib and everolimus together can help treat kidney cancer. One study found that patients lived about 15.7 months without their cancer worsening, compared to 10.2 months with a different treatment. This indicates the combination helped patients live longer without cancer progression. Another study found that about 22% of patients experienced a noticeable decrease in tumor size. Although no patients became completely cancer-free, the treatment stabilized the disease in nearly 20% of cases. This suggests that lenvatinib and everolimus may effectively manage kidney cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Yousef Zakharia, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

Adults with advanced or metastatic renal cell carcinoma, clear cell type, who may undergo surgery. They must have normal kidney function or mild impairment, acceptable blood counts and liver enzymes, an ECOG performance status of 0-2 (meaning they can care for themselves), a life expectancy over 12 weeks, measurable disease by medical imaging, and a heart ejection fraction ≥45%. Men and women must use contraception; women need a negative pregnancy test.

Inclusion Criteria

Your liver function test results (AST/ALT) are within the normal range.

I am not pregnant and agree to use two forms of birth control.

I am a man who can father a child and agree to use birth control.

Exclusion Criteria

Your cholesterol and triglyceride levels are very high when you haven't eaten for a while.

Subject that is pregnant or lactating

I have been cancer-free from another type for less than 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person)

Treatment

Participants receive lenvatinib and everolimus for 8 weeks, followed by a 1-week washout period

9 weeks

Weekly visits (in-person)

Surgery

Participants undergo nephrectomy surgery after the washout period

1 week

1 visit (in-person)

Follow-up

Participants are monitored for surgical complications and disease status

5 years

Monthly visits if metastatic disease, every three months if no evidence of disease

What Are the Treatments Tested in This Trial?

Interventions

• Everolimus
• Lenvatinib
• Partial or Radical Cytoreductive Nephrectomy

Trial Overview The trial is testing the combination of two drugs: lenvatinib plus everolimus in patients with local and metastatic renal cell carcinoma. The goal is to see if this drug combo can shrink tumors enough to make them operable when they previously weren't considered so.

How Is the Trial Designed?

Group I: Lenvatinib and Everolimus prior to cytoreductive nephrectomy Experimental Treatment 3 Interventions

Eligible patients will start treatment with lenvatinib 18 mg PO daily (administered as one 10 mg capsule and two 4 mg capsules) and everolimus 5 mg PO daily for 4 weeks constituting one cycle. Two cycles of treatment will be administered and after 2 weeks wash out period, the patients will go for nephrectomy.

Everolimus is already approved in United States, European Union for the following indications:

Approved in United States as Afinitor for:

• Advanced renal cell carcinoma
• Subependymal giant cell astrocytoma
• Progressive neuroendocrine tumors of pancreatic origin
• Advanced hormone receptor-positive, HER2-negative breast cancer
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in European Union as Votubia for:

• Subependymal giant cell astrocytoma
• Renal angiomyolipoma
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in United States as Zortress for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Yousef Zakharia

Lead Sponsor

Trials

5

Recruited

160+

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2035716

Lenvatinib plus Pembrolizumab or Everolimus for ... Lenvatinib plus pembrolizumab was associated with significantly longer progression-free survival and overall survival than sunitinib.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33792094/

Lenvatinib with or Without Everolimus in Patients ... - PubMed One patient (1.8%) achieved a complete response, and 11 patients (20.0%) achieved a partial response, for an overall response rate (ORR) of 21.8%; 35 patients ( ...

3. urologytimes.com urologytimes.com/view/contemporary-rcc-trial-adds-fresh-lenvatinib-everolimus-pfs-perspective

Contemporary RCC trial adds fresh lenvatinib/everolimus ... The median progression-free survival was 15.7 months with the combination of lenvatinib plus everolimus compared with 10.2 months with ...

4. lenvimahcp.com lenvimahcp.com/2nd-line-advanced-renal-cell-carcinoma/efficacy-results

NCCN recommendation - LENVIMA ® (lenvatinib) In RCC (renal cell carcinoma), hypertension occurred in 42% of patients on LENVIMA + everolimus (13% grade 3). Systolic blood pressure ≥160 mmHg occurred in 29% ...

5. actionkidneycancer.org actionkidneycancer.org/lenvatinib-plus-everolimus-for-patients-with-metastatic-kidney-cancer/

Lenvatinib plus everolimus for patients with metastatic ... There were no complete responses and nearly 2 in 10 patients had stable disease. The average overall survival time was was just over 11 months ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33867192/

A Single-arm, Multicenter, Phase 2 Study of Lenvatinib ... Conclusions: Lenvatinib plus everolimus showed promising anticancer activity in patients with advanced nccRCC with an ORR of 26% and is worthy of further study.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03173560

Trial to Assess Safety and Efficacy of Lenvatinib (18 mg vs. ... Trial to Assess Safety and Efficacy of Lenvatinib (18 mg vs. 14 mg) in Combination With Everolimus in Participants With Renal Cell Carcinoma. ClinicalTrials.gov ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.489

Efficacy and safety of lenvatinib plus everolimus in ... Adverse events were significant: 54.9% required dose reductions of LEN, and 25.6% experienced treatment interruptions. For EVE, 17.1% required ...

9. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)04953-1/fulltext

A multicenter randomized phase II trial of lenvatinib plus ... A total of 60 PFS events were observed. Median PFS was 15.7 months with lenvatinib + everolimus and 10.2 months with cabozantinib (hazard ratio ...