A Randomized, Open-label (formerly Double-blind), Phase 2 Trial to invistagate how safe and how efficacious Lenvatinib is at two different starting doses (18 mg vs. 14 mg QD) when it is given in Combination with Everolimus (5 mg once a day ) in patients with Renal cancer that have already had one VEGF-Targeted Treatment
- Conditions
- Advanced renal cell carcinomaMedDRA version: 21.0Level: PTClassification code 10038389Term: Renal cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10038409Term: Renal cell carcinoma NOSSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002778-11-GB
- Lead Sponsor
- Eisai Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 338
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.
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 149
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 189
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 or cardiac arrhythmia associated with significant cardiovascular impairment or left ventricular ejection fraction (LVEF)below the institutional normal range as determined by screening multiple- gated 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 investigator(s) would preclude the subject’s participation in a clinical study.
18. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human c
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