NCT03324373

Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC)

Proof of Concept for Lenvatinib and Everolimus Prior to Nephrectomy in Eligible Patients With Local and Metastatic Renal Cell Carcinoma (RCC)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 11 (actual)
• Sponsor: Yousef Zakharia · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this research study is to see what effect the combination of lenvatinib plus everolimus has in local and metastatic renal cell carcinoma to potentially make surgically unresectable tumors resectable.

Detailed description

This is a pilot interventional clinical trial at the University of Iowa Hospitals and Clinics, enrolling 15 subjects and lasting approximately 12 months. 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 (8 weeks) will be administered followed by a 1-week wash out period during which time patients will be evaluated by the urology oncology team and appropriate surgery will be planned. The wash out period is for drug to be eliminated prior to surgery, to avoid bleeding/wound healing effects. This includes partial nephrectomy or radical nephrectomy. Following surgery, patients with no evidence of disease will have active surveillance. Patients who continue to have disease following surgery will receive further systemic treatment for metastatic disease.

Conditions

• Renal Cell Carcinoma

Interventions

Type	Name	Description
DRUG	Lenvatinib	Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). Lenvatinib also inhibits other RTKs that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1, 2, 3, and 4; the platelet derived growth factor receptor alpha (PDGFRα), KIT, and RET.
DRUG	Everolimus	Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers. Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation (mTORC1) and thus inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis. In addition, everolimus inhibited the expression of hypoxia-inducible factor (e.g., HIF-1) and reduced the expression of vascular endothelial growth factor (VEGF). Inhibition of mTOR by everolimus has been shown to reduce cell proliferation, angiogenesis, and glucose uptake in in vitro and/or in vivo studies.
PROCEDURE	Partial or Radical Cytoreductive Nephrectomy	Surgical removal of a kidney. After completion of 8 weeks of therapy and restaging, investigators will require 2 weeks wash out period. The patients will be evaluated by urology oncology team and appropriate surgery will be planned. This includes partial nephrectomy and radical nephrectomy.

Timeline

• Start date: 2019-03-20
• Primary completion: 2023-09-27
• Completion: 2024-08-28
• First posted: 2017-10-27
• Last updated: 2025-04-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study