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
- Conditions
- Advanced Renal Cell CarcinomaMedDRA 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-IT
- Lead Sponsor
- EISAI LIMITED
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 735
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 defined as calculated creatinine clearance =
30 mL/min per the Cockcroft and Gault formula.
8. Adequate bone marrow function defined by:
• Absolute neutrophil count (ANC) =1500/mm3
• Platelets =100,000/mm3
• Hemoglobin =9 g/dL.
9. Adequate blood coagulation function defined by International
Normalized ratio (INR) =1.5 (except for subjects on warfarin therapy
where INR must be =3.0 prior to randomization).
10. Adequate liver function defined by:
• Total bilirubin =1.5 times the upper limit of normal (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 times the 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 332
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 403
1. Subjects 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. Subjects 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. Any signs (eg, radiologic) or symptoms of brain
metastases must be stable for at least 4 weeks before starting study
treatment.
3. Active malignancy (except 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 and there is 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. Subjects 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). Note: The killed virus vaccines used for
seasonal influenza vaccines for injection are allowed; however intranasal
influenza vaccines (eg, FluMist®) are live attenuated vaccines and are
not allowed within 30 days of C1D1.
7. Subjects with proteinuria >1+ on urine dipstick testing will undergo
24-h urine collection for quantitative assessment of proteinuria.
Subjects 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. Subjects 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 significant hemoptysis or tumor bleeding within 2 weeks
prior to the first dose of study drug.
15. Significant cardiovascular impairment within 6 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 or stroke, cardiac arrhythmia associated with significant
cardiovascular impairment, or a left ventricular ejection fraction (LVEF)
below the institutional normal range as de
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method