Clinical Trials /

Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC)

NCT03324373

Description:

The purpose of this research study is to see what effect the combination of lenvatinib plus everolimus has on the tumors in patients with locally advanced and metastatic renal cell carcinoma, prior to cytoreductive nephrectomy.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Lenvatinib and Everolimus in Renal Cell Carcinoma (RCC)
  • Official Title: Proof of Concept for Lenvatinib and Everolimus Prior to Cytoreductive Nephrectomy in Eligible Patients With Locally Advanced and Metastatic Renal Cell Carcinoma (RCC)

Clinical Trial IDs

  • ORG STUDY ID: 201710801
  • NCT ID: NCT03324373

Conditions

  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
LenvatinibLENVIMA®, KISPLYX®Lenvatinib and Everolimus prior to cytoreductive nephrectomy
EverolimusAFINITOR®Lenvatinib and Everolimus prior to cytoreductive nephrectomy

Purpose

The purpose of this research study is to see what effect the combination of lenvatinib plus everolimus has on the tumors in patients with locally advanced and metastatic renal cell carcinoma, prior to cytoreductive nephrectomy.

Detailed Description

      This is a Phase I interventional clinical trial, with an expansion cohort, at the University
      of Iowa Hospitals and Clinics enrolling 15 subjects and lasting approximately 12 months.
      Eligible patients will be treated with lenvatinib and everolimus for 8 weeks prior to
      cytoreductive nephrectomy. A wash out period of 2 weeks is needed between the end of
      treatment and surgery.

      Eligible patients will start treatment with lenvatinib 18 milligrams (mg) orally (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.
    

Trial Arms

NameTypeDescriptionInterventions
Lenvatinib and Everolimus prior to cytoreductive nephrectomyExperimentalEligible 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
  • Everolimus

Eligibility Criteria

        Inclusion Criteria:

          1. Histogically confirmed locally advanced or metastatic renal cell carcinoma, clear cell
             histology that can be considered for cytoreductive nephrectomy.

          2. The 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

          3. Written and voluntary informed consent.

          4. 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).

          5. AST/ALT <2.5 X institutional upper limit of normal

          6. Adequate hematological lab values including:

               -  Absolute Neutrophil count (ANC) ≥ 1.0 x 109/L

               -  Platelets ≥ 100 x 109/L

               -  Hemoglobin ≥ 8.0 g/dL

          7. 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).

          8. Age of at least 18 years.

          9. Life expectancy of 12 weeks or more.

         10. Measurable disease per RECIST criteria.

         11. Ejection fraction (EF) ≥ 45%

         12. 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).

         13. 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.

         14. Abstinence is acceptable if this is the usual lifestyle and preferred contraception
             for the patient.

        Exclusion Criteria:

          1. Any other cancer from which the patient has been disease-free for less than 5 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).

          2. Symptomatic untreated metastases in the central nervous system.

          3. Subject that is pregnant or lactating.

          4. Pre-existing uncontrolled hypertension defined as >140/90 mm Hg with medication.

          5. Known HIV or acquired immunodeficiency syndrome-related disease.

          6. Prolongation of QTc interval (>480 ms). QTc interval per Bazett formula.

          7. Uncontrolled diabetes [fasting glucose >1.5 × upper limit of normal (ULN)],

          8. Fasting total cholesterol >300 mg/dL and fasting triglyceride levels >2.5 × ULN

          9. Proteinuria (defined by >2gm/ 24 hours urine protein if urinalysis is >2+)

         10. 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.

        12. 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)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description: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)
Measure:Comparison of surgical outcomes to historical controls
Time Frame:Within two years following the last study participant's surgery
Safety Issue:
Description:Review estimated blood loss, blood transfusion, operative time, adjacent organ injury, and postoperative complications.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yousef Zakharia

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