Renal Cell CarcinomaPhase 1NCT03324373
Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC)
A Phase 1 study testing Lenvatinib, Everolimus and Partial or Radical Cytoreductive Nephrectomy in people with Renal Cell Carcinoma, run by Yousef Zakharia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Renal Cell Carcinoma
- What is being tested?
- Lenvatinib, Everolimus and Partial or Radical Cytoreductive Nephrectomy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Mar 2019to 28 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed locally advanced or metastatic renal cell carcinoma, clear cell histology that can be considered for partial or complete nephrectomy.
- Locally advanced disease is defined as follows:
- Adjacent organs (T4) or vascular invasion (Level III/ IV / IVC thrombus)
- Bulky lymphadenopathy encasing renal or great vessels
- cT1b-T2a Grade (G) 4, cT2b G3/4, c T3-cT4 any grade and any cT with cN1 or M1 disease
- Written and voluntary informed consent.
Show all 20Show fewer
- Renal function (creatinine level within normal institutional limit, or creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula).
- AST/ALT <2.5 X institutional upper limit of normal
- Adequate hematological lab values including:
- Absolute Neutrophil count (ANC) ≥ 1.0 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 8.0 g/dL
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 (fully active, able to carry on all pre-disease performance without restriction), 1 (restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, such as light housework or office work) or 2 (Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours).
- Age of at least 18 years.
- Life expectancy of 12 weeks or more.
- Measurable disease per RECIST criteria.
- Ejection fraction (EF) ≥ 45%
- Female patients of childbearing potential, as defined in this protocol, must have a negative urine or serum pregnancy test within 72 hours prior to taking the first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative then a serum test is required which must be negative for the patient to enroll. Women of childbearing potential (WOCBP) must be willing to use 2 medically acceptable methods of contraceptive from Day 1 through 120 days after the last dose of trial treatment. The 2 medically acceptable birth control methods can be either 2 barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide as per local regulations or guidelines. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents).
- Male patients of childbearing potential, as described in this protocol, must agree to use an adequate method of contraception from Day 1 through 120 days after the last dose of trial treatment.
- Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the patient.
Who cannot join
- Any other cancer from which the patient has been disease-free for less than 3 years (except treated and cured basal-cell or squamous-cell skin cancer, superficial bladder cancer, or treated carcinoma in situ of the cervix, breast, or bladder and treated localized prostate cancer with undetectable PSA for 2 years).
- Symptomatic untreated metastases in the central nervous system.
- Subject that is pregnant or lactating.
- Pre-existing uncontrolled hypertension defined as >140/90 mm Hg with medication.
- Known HIV or acquired immunodeficiency syndrome-related disease.
- Prolongation of QTc interval (>480 ms). QTc interval per Bazett formula.
Show all 11Show fewer
- Uncontrolled diabetes [fasting glucose >1.5 × upper limit of normal (ULN)] (it will be acceptable if labs were done non-fasting and met the fasting requirement (meaning glucose < 1.5 ULN).
- Fasting total cholesterol >300 mg/dL and fasting triglyceride levels >2.5 × ULN (it will be acceptable if labs were done non-fasting and met the fasting requirement (meaning total cholesterol <300 mg/dL and triglyceride levels < 2.5 × ULN.
- Proteinuria (defined by urine protein/creatinine ratio (UPC) >2.0 if urinalysis protein is >2+)
- Significant cardiovascular impairment: History of (a) congestive heart failure greater than New York Heart association (NYHA) Class II, (b) unstable angina, (c) myocardial infarction (d) stroke, or (e) cardiac arrhythmia associated with hemodynamic instability within 6 months of the first dose of study drugs.
- Known history of active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] RNA detected)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52242
About this study
Official title: Proof of Concept for Lenvatinib and Everolimus Prior to Nephrectomy in Eligible Patients With Local and Metastatic Renal Cell Carcinoma (RCC)
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.
Read the 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
- Being tested
- Lenvatinib, Everolimus, Partial or Radical Cytoreductive Nephrectomy
- Medical subject headings
- Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenvatinibDrug
Also called LENVIMA®, KISPLYX®
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.
EverolimusDrug
Also called AFINITOR®
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.
Partial or Radical Cytoreductive NephrectomyProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| Lenvatinib and Everolimus prior to cytoreductive nephrectomy | Experimental | 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. Receives: Drug: Lenvatinib; Drug: Everolimus; Procedure: Partial or Radical Cytoreductive Nephrectomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Surgical complications as assessed by Clavien-Dindo classification system
To determine whether there is increased surgical morbidity with lenvatinib and everolimus prior to nephrectomy as assessed by Clavien complications.
Measured: Assessment will be completed at the first post-operative visit within 4-6 weeks after surgery.
Secondary outcomes (3)
Treatment related adverse events as assessed by CTCAE criteria, version 4.03
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.
Measured: First treatment through 5 years after Cycle 1, Day 1 or death.
Changes in overall response rate as assessed by RECIST 1.1
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)
Measured: 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.
Comparison of surgical outcomes to historical controls
Review estimated blood loss, blood transfusion, operative time, adjacent organ injury, and postoperative complications.
Measured: Within two years following the last study participant's surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2017
- Study start20 Mar 2019
- Primary completion27 Sep 2023
- Study completion28 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Cell CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yousef Zakharia
- Sponsor type
- University, hospital or other
- Collaborators
- Eisai Inc.
- Responsible party
- Sponsor-investigator, Yousef Zakharia, University of Iowa
- Investigators
- Yousef Zakharia, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03324373
- Sponsor's protocol ID
- 201710801
- Status last verified
- Apr 2025
- First submitted
- 20 Oct 2017
- Last updated
- 24 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proof of Concept for Lenvatinib and Everolimus Prior to Nephrectomy in Eligible Patients With Local and Metastatic Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT03324373
- Acronym / sponsor ID
- 201710801
- Conditions
- Renal Cell Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Yousef ZakhariaUniversity, hospital or other
- Collaborators
- Eisai Inc.
- Study start
- 20 Mar 2019 (actual)
- Primary completion
- 27 Sep 2023 (actual)
- Study completion
- 28 Aug 2024 (actual)
- First posted
- 27 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenvatinib and Everolimus prior to cytoreductive nephrectomy | Experimental | Drug: Lenvatinib, Drug: Everolimus, Procedure: Partial or Radical Cytoreductive NephrectomyEligible 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Histologically confirmed locally advanced or metastatic renal cell carcinoma, clear cell histology that can be considered for partial or complete nephrectomy.
- cT1b-T2a Grade (G) 4, cT2b G3/4, c T3-cT4 any grade and any cT with cN1 or M1 disease
- Written and voluntary informed consent.
- Renal function (creatinine level within normal institutional limit, or creatinine clearance >30 mL/min/1.73 m2 for patients with creatinine levels above institutional normal, calculated using the Cockcroft-Gault formula).
- AST/ALT <2.5 X institutional upper limit of normal
Key exclusion criteria (11 listed)
- Any other cancer from which the patient has been disease-free for less than 3 years (except treated and cured basal-cell or squamous-cell skin cancer, superficial bladder cancer, or treated carcinoma in situ of the cervix, breast, or bladder and treated localized prostate cancer with undetectable PSA for 2 years).
- Symptomatic untreated metastases in the central nervous system.
- Subject that is pregnant or lactating.
- Pre-existing uncontrolled hypertension defined as >140/90 mm Hg with medication.
- Known HIV or acquired immunodeficiency syndrome-related disease.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LenvatinibAlso: LENVIMA®, KISPLYX®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 | Lenvatinib and Everolimus prior to cytoreductive nephrectomy |
| EverolimusAlso: AFINITOR®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. | Drug | Lenvatinib and Everolimus prior to cytoreductive nephrectomy |
| Partial or Radical Cytoreductive NephrectomySurgical 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. | Procedure or surgery | Lenvatinib and Everolimus prior to cytoreductive nephrectomy |
Primary outcome
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.
3 secondary outcomes
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.
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.
Comparison of surgical outcomes to historical controls
Time frame: Within two years following the last study participant's surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2025.
- Individual participant dataSharing planned: No
Related trials for Renal Cell Carcinoma
RecruitingPhase 1/2
Study of INBRX-106 and INBRX-106 in Combination With Pembrolizumab (Keytruda®) in Subjects With Locally Advanced or Metastatic Solid Tumors (Hexavalent OX40 Agonist)
Solid Tumor, Non-Small Cell Lung Cancer
Active, not recruitingPhase 3
A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011)
Carcinoma, Renal Cell
RecruitingPhase 2/3
Testing the Role of DNA Released From Tumor Cells Into the Blood in Guiding the Use of Immunotherapy After Surgical Removal of the Bladder, Kidney, Ureter, and Urethra for Urothelial Cancer Treatment, MODERN Study
Muscle Invasive Bladder Urothelial Carcinoma, Muscle Invasive Renal Pelvis Urothelial Carcinoma
Not yet recruitingPhase 2
Toripalimab and Lenvatinib With or Without SBRT Before Surgery for Non-Clear Cell Kidney Cancer
Nonmetastatic Locally Advanced Non-Clear Cell Renal Cell Carcinoma
Not yet recruitingPhase 2
Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma
Localized Clear Cell Renal Cell Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yousef Zakharia, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Lenvatinib, Everolimus and Partial or Radical Cytoreductive Nephrectomy in people with Renal Cell Carcinoma, run by Yousef Zakharia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.