A Clinical Trial to Compare How Well Lenvatinib Works in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in Patients with Kidney Cancer that has Spread and Who Have Not Previously Been Treated With Anti-Cancer Medicines

Phase 1

• Conditions: Advanced Renal Cell Carcinoma; MedDRA version: 21.1Level: PTClassification code 10050513Term: Metastatic renal cell carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-000916-14-AT
• Lead Sponsor: Eisai Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-03-07
• Last Update Posted: 24 January 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1050

Inclusion Criteria

1. Histological or cytological confirmation of RCC with a clear-cell component (original tissue diagnosis of RCC is acceptable).
2. Documented evidence of advanced RCC.
3. At least 1 measurable target lesion according to RECIST 1.1 meeting the following criteria:
• Lymph node (LN) lesion that measures at least 1 dimension as =1.5 cm in the short axis
• Non-nodal lesion that measures =1.0 cm in the longest diameter
•The lesion is suitable for repeat measurement using computerized tomography/magnetic resonance imaging (CT/MRI). Lesions that have had external beam radiotherapy (EBRT) or locoregional therapy must show radiographic evidence of disease progression based on RECIST 1.1 to be deemed a target lesion.
4. Male or female subjects age =18 years (or any age greater than 18 years of age if that age is considered to be an adult per the local jurisdiction) at the time of informed consent
5. Karnofsky Performance Status (KPS) of =70.
6. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP =150/90 mmHg at Screening and no change in antihypertensive medications within 1 week before the Cycle 1/Day 1.
7. Adequate renal function as creatinine =1.5× upper limit of normal
(ULN); or for subjects with creatinine >1.5×ULN, the calculated
creatinine clearance =30 mL/min (per the Cockcroft-Gault formula) is
acceptable.
8.Adequate bone marrow function defined by:
•Absolute neutrophil count (ANC) =1500/mm3
•Platelets =100,000/mm3
•Hemoglobin =9 g/dL
NOTE: Criteria must be met without erythropoietin dependency and
without packed red blood cell (pRBC) transfusion within the previous 2
weeks.
9.Adequate blood coagulation function defined by International
Normalized ratio (INR) =1.5 unless participant is receiving anticoagulant
therapy, as long as INR is within therapeutic range of intended use of
anticoagulants.
10.Adequate liver function defined by:
•Total bilirubin =1.5×ULN except for unconjugated hyperbilirubinemia of
Gilbert's syndrome.
•Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and
aspartate aminotransferase (AST) =3×ULN (in the case of liver
metastases =5×ULN), unless there are bone metastases. Subjects with
ALP values >3×ULN and known to have bone metastases can be
included.
11. Provide written informed consent.
12. Willing and able to comply with all aspects of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 580
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 470

Exclusion Criteria

1. Subj. who have received any systemic anticancer therapy for RCC,
including anti-VEGF therapy, or any systemic investigational anticancer
agent. Prior adjuvant treatment with an investigational anticancer agent
is not allowed unless the investigator can provide evidence of subject's
randomization to placebo arm.
2. Subj. with CNS metastases are not eligible, unless they have
completed local therapy (eg, whole brain radiation therapy [WBRT],
surgery or radiosurgery) and have discontinued the use of
corticosteroids for this indication for at least 4 weeks before starting
treatment in this study.
3. Active malignancy (ex. for RCC, definitively treated basal or squamous cell carcinoma of the skin, and carcinoma in-situ of the cervix
or bladder) within the past 24 months. Subjects with history of localized
& low risk prostate cancer are allowed in the study if they were treated
with curative intent if no PSA recurrence within the past 5 years.
4. Prior radiation therapy within 21 days prior to start of study treatment
with the exception of palliative radiotherapy to bone lesions, which is
allowed if completed 2 weeks prior to study treatment start.
5. Subj. who are using other investigational agents or who had
received investigational drugs =4 weeks prior to study treatment start.
6. Received a live vaccine within 30 days of planned start of study
treatment (Cycle 1/Day 1). Examples of live vaccines include, measles,
mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies,
Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal
influenza vaccines for injection are generally killed virus vaccines and
are allowed; however, intranasal influenza vaccines (eg, FluMist®) are
live attenuated vaccines and are not allowed.
7. Subj. with proteinuria >1+ on urine dipstick testing will undergo
24-h urine collection for quantitative assessment of proteinuria.
Subj. with urine protein =1 g/24 h will be ineligible
8. Fasting total cholesterol >300 mg/dL (or >7.75 mmol/L) and/or
fasting triglycerides level >2.5 x ULN. NOTE: these subjects can be
included after initiation or adjustment of lipid-lowering medication.
9. Uncontrolled diabetes as defined by fasting glucose >1.5 times the
ULN. Note: these subjects can be included after initiation or adjustment
of glucose-lowering medication.
10. Prolongation of QTc interval to >480 ms.
11. Subj.who have not recovered adequately from any toxicity
and/or complications from major surgery prior to starting therapy.
12. Gastrointestinal malabsorption, gastrointestinal anastomosis, or any
other condition that might affect the absorption of lenvatinib,
everolimus, and/or sunitinib.
13. Bleeding or thrombotic disorders or subjects at risk for severe
hemorrhage. The degree of tumor invasion/infiltration of major blood
vessels (eg, carotid artery) should be considered because of the
potential risk of severe hemorrhage associated with tumor
shrinkage/necrosis following lenvatinib therapy.
14. Clinically signif. hemoptysis or tumor bleeding within 2 weeks
prior to the first dose of study drug.
15. Signif. cardiovascular impairment within 12 months of the first
dose of study drug: history of congestive heart failure greater than New
York Heart Association (NYHA) Class II, unstable angina, myocardial
infarction, cerebrovascular accident (CVA), or cardiac arrhythmia
associated with hemodynamic instability.
The following is also excluded:
•Left ventricular ejection fraction (LVEF) below the institutional no

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified