Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC)
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|ClinicalTrials.gov Identifier: NCT03324373|
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : May 6, 2022
|Condition or disease||Intervention/treatment||Phase|
|Renal Cell Carcinoma||Drug: Lenvatinib Drug: Everolimus Procedure: Partial or Radical Cytoreductive Nephrectomy||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Proof of Concept for Lenvatinib and Everolimus Prior to Nephrectomy in Eligible Patients With Local and Metastatic Renal Cell Carcinoma (RCC)|
|Actual Study Start Date :||March 20, 2019|
|Estimated Primary Completion Date :||April 30, 2023|
|Estimated Study Completion Date :||April 30, 2024|
Experimental: Lenvatinib and Everolimus prior to cytoreductive nephrectomy
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.
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.
Other Name: LENVIMA®, KISPLYX®
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.
Other Name: AFINITOR®
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.
- Surgical complications as assessed by Clavien-Dindo classification system [ Time Frame: Assessment will be completed at the first post-operative visit within 4-6 weeks after surgery. ]To determine whether there is increased surgical morbidity with lenvatinib and everolimus prior to nephrectomy as assessed by Clavien complications.
- Treatment related adverse events as assessed by CTCAE criteria, version 4.03 [ Time Frame: First treatment through 5 years after Cycle 1, Day 1 or death. ]To assess whether patients will tolerate the combination of lenvatinib and everolimus prior to surgery with same rate of toxicities as seen in prior Phase II clinical trials.
- Changes in overall response rate as assessed by RECIST 1.1 [ Time Frame: Screening (within 14 days of Day 1) and pre-surgery (week 9-10). 1) If metastatic disease followup monthly or 2) if no evidence of disease followup every three months until five years or death. ]Response and progression will be evaluated using RECIST 1.1. Changes in the largest diameter (unidimensional measurement) of the tumor lesions and the shortest diameter in the case of malignant lymph nodes are used in the criteria. Imaging includes conventional computed tomography (CT) and/or magnetic resonance imagining (MRI), bone scan, and positron emission tomography-computed tomography (PET-CT)
- Comparison of surgical outcomes to historical controls [ Time Frame: Within two years following the last study participant's surgery ]Review estimated blood loss, blood transfusion, operative time, adjacent organ injury, and postoperative complications.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324373
|Contact: Yousef Zakharia, MDfirstname.lastname@example.org|
|United States, Iowa|
|University of Iowa Hospitals and Clinics||Recruiting|
|Iowa City, Iowa, United States, 52242|
|Contact: Yousef Zakharia, MD 319-384-8076 email@example.com|
|Principal Investigator:||Yousef Zakharia, MD||University of Iowa|