A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination with Everolimus or Pembrolizumab Versus Sunitinib Alone in First-Line Treatment of Subjects with Advanced Renal Cell Carcinoma (CLEAR).
- Conditions
- Advanced Renal Cell CarcinomaKindney Cancer10038363
- Registration Number
- NL-OMON54767
- Lead Sponsor
- Eisai
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 15
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.
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 x 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 >3xULN 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.
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). 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 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 wi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>• Progression-free survival (PFS) by independent review is defined as the time<br /><br>from the date of randomization to the date of the first documentation of<br /><br>disease progression or death (whichever occurs first) as determined by IIR<br /><br>using RECIST 1.1. PFS censoring rules will follow the FDA guidance of 2007;<br /><br>specifics of this will be detailed in the Statistical Analysis Plan.</p><br>
- Secondary Outcome Measures
Name Time Method