A Randomized, Open-label (formerly Double-Blind), Phase 2 Trial to Assess Safety and Efficacy of Lenvatinib at Two Different Starting Doses (18 mg vs. 14 mg QD) in Combination with Everolimus (5 mg QD) in Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment
- Conditions
- Renal Cell Carcinomarenal-cell cancer1003836410038430
- Registration Number
- NL-OMON50669
- Lead Sponsor
- Eisai
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 13
1. Histological or cytological confirmation of predominant clear cell RCC
(original tissue diagnosis of RCC is acceptable)., 2. Documented evidence of
advanced RCC., 3. One prior disease progression episode on or after
VEGF-targeted treatment (for example, but not limited to, sunitinib, sorafenib,
pazopanib, cabozantinib, bevacizumab, axitinib, vatalanib, AV951/tivozanib)
administered for the treatment of RCC. Prior PD-1/PD-L1 treatment in addition
to 1 prior VEGF-targeted treatment is allowed., 4. 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., 5. Male or
female subjects age *18 years (or any age >18 years if that age is
considered to be an adult per the local jurisdiction) at the time of informed
consent., 6. Karnofsky Performance Status (KPS) of *70., 7. 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 Cycle 1/Day 1., 8. Adequate renal function
defined as calculated creatinine clearance *30 mL/min per the Cockcroft and
Gault formula (Appendix 1)., 9. Adequate bone marrow function defined by:,
Absolute neutrophil count (ANC) *1500/mm3 (*1.5 x 109/L) Platelets *100,000/
mm3(*100 x 109/L) Hemoglobin *9 g/dL., 10. 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)., 11. Adequate
liver function defined by:, Total bilirubin *1.5 times the 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). Subjects with bone metastases
with ALP values greater than 3 times can be included., 12. Subject must
voluntarily agree to provide written informed consent., 13. Subject must be
willing and able to comply with all aspects of the protocol.
1. More than 1 prior VEGF-targeted treatment for advanced RCC., 2. Subjects
with Central Nervous System (CNS) metastases are not eligible, unless they have
completed local therapy for at least 4 weeks and have discontinued the use of
corticosteroids for this indication or are on a tapering regimen of
corticosteroids (defined as *10 mg prednisolone equivalent) 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 or definitively treated basal
or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix or
bladder) within the past 24 months., 4. Any anti-cancer treatment (except for
radiation therapy, see exclusion #5) within 21 days, or any investigational
agent within 30 days prior to the first dose of study drug; subjects should
have recovered from any toxicity related to previous anti-cancer treatment to
CTC grade 0 or 1., 5. 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., 6. Known
intolerance to study drug (or any of the excipients) and/or known
hypersensitivity to rapamycins (eg, sirolimus, everolimus, temsirolimus) or any
of the excipients., 7. Subjects with proteinuria > 1 + on urinalysis 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 or everolimus., 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 prior to 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
left ventricular ejection fraction (LVEF) below the institutional normal range
as determined by screening multigated acquisition (MUGA) scan or
echocardiogram., 16. Active infection (any infection requiring systemic
treatment)., 17.Any medical or other condition that in the opinion of the
in
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoints<br /><br>* Objective response rate (ORR) at Week 24 (ORR24W) as assessed by the<br /><br>investigator according to RECIST 1.1. ORR24W is defined as the proportion of<br /><br>subjects with best overall response (BOR) of complete response (CR) or partial<br /><br>response (PR) at the Week¬24 (after randomization) time point or earlier. To<br /><br>be considered a BOR, all responses must be confirmed no less than 4 weeks after<br /><br>the initial assessment of response.<br /><br><br /><br>* Proportion of subjects with intolerable Grade 2 and any * Grade 3 TEAEs<br /><br>within 24 weeks after randomization (as of the Week-24 time point).</p><br>
- Secondary Outcome Measures
Name Time Method