An early phase trial studying how well E7080 works in treating patients with advanced kidney cancer which has spread to other parts of the body. The first part of the trial will study the combination of E7080 and everolimus. The second part will compare the treatments when given alone and when given in combination. The trial is taking place worldwide, patients know if they are receiving the study drug alone, in combination with everolimus or if they are recieving everolimus alone.

Phase 1

• Conditions: nresectable Advanced or Metastatic Renal Cell Carcinoma; MedDRA version: 18.0Level: PTClassification code 10038414Term: Renal cell carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 18.0Level: 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: EUCTR2010-019484-10-PL
• Lead Sponsor: Eisai Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-10-17
• Last Update Posted: 30 April 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

1) Histologically confirmed diagnosis of renal cell carcinoma. 2) Phase 1: Disease progression after prior vascular endothelial growth factor (VEGF)-targeted treatment. 3) Phase 2: Histological or cytological confirmation of predominant clear cell RCC (original tissue diagnosis of RCC is acceptable). 4) Documented evidence of unresectable advanced or metastatic RCC. 5) Phase 2: Radiographic evidence of disease progression according to RECIST 1.1 on or within 9 months of stopping prior therapy. 6) Phase 2: One prior disease
progression episode on or after vascular endothelial growth factor (VEGF)-targeted treatment (for example, but not limited to, sunitinib, sorafenib, pazopanib, bevacizumab, axitinib, vatalanib, AV951/ tivozanib) for unresectable advanced or metastatic RCC (not including disease progression after VEGF-targeted adjuvant treatment). 7) Phase 2: Measurable disease meeting the following criteria:
a) At least 1 lesion of = 1.5 cm in the longest diameter for a non-lymph node or = 1.5 cm in the short-axis diameter for a lymph node which is serially measurable according to RECIST 1.1 using computerized tomography /magnetic resonance imaging (CT/MRI) or photography b) Lesions that have had external beam radiotherapy (EBRT) or loco-regional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
8) Subjects must have an ECOG Performance Status of 0 or 1.
9) Adequately controlled blood pressure with or without antihypertensive medications, defined as BP = 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to Cycle 1 Day 1 10) Adequate renal function defined as calculated creatinine clearance = 30 mL/min. 11) Adequate bone marrow function:
- Absolute neutrophil count (ANC) = 1500/mm3 (= 1.5 x 103/µL);
- Platelets = 100,000/mm3 (= 100 x 109/L);
- Hemoglobin = 9.0 g/dL.
12) Adequate blood coagulation function 13) Adequate liver function:
- Bilirubin = 1.5 x the upper limit of normal (ULN) except for unconjugated hyperbilirubinaemia of Gilbert’s syndrome;
- Alkaline phosphatase, alanine aminotransferase (ALT), and aspartateaminotransferase (AST) = 3 times ULN (= 5 x ULN if subject has liver metastases). 14) Males or females age = 18 years at the time of informed consent. 15) All females must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of beta-human chorionic gonadotropin [ß-hCG]) at the Screening Visit (and/or within 72 hours of the first dose of study drug). Females of child-bearing potential, if not practicing total abstinence or have a vasectomised partner with confirmed azoospermia, must agree to use two highly effective methods of contraception ( e.g., 1), abstinence, an intrauterine device [IUD], or intrauterine system (IUS); 2) a barrier method such as condom or occlusive cup (diaphragm or cervical/vault caps) + spermicide (foam, gel, cream, etc.) 3) oral, injected, or implanted hormonal contraceptives throughout the entire study period and for 30 days after study drug discontinuation. Use of a double-barrier method (i.e., use at the same time of a condom + occlusive cup [diaphragm or cervical/vault caps] + spermicide [foam, gel, cream, etc.]) is accepted as two highly effective methods of contraception. The only subjects who will be exempt from this requirement are postmenopausal women (defined as women who have been amenorrheic for at least 1

Exclusion Criteria

1) Phase 1b or Phase 2 specific per below:
- Phase 1b only: Subjects with untreated or unstable metastases to the CNS are excluded. Subjects who have completed local therapy and have discontinued the use of steroids for this indication at least 4 weeks prior to commencing treatment
and in whom stability has been proven by at least 2 CT or MRI scans obtained at least 4 weeks apart are eligible for Phase 1b only.
- Phase 2 only: subjects with CNS (eg, brain or leptomeningeal) metastases are excluded.
2) Phase 2 only: More than one prior disease progression episode on or after VEGF-targeted treatment for unresectable advanced or metastatic RCC (not including disease progression after VEGF-targeted adjuvant treatment).
3) Phase 1b or Phase 2 specific per below:
- Phase 1b only: Prior exposure to E7080
- Phase 2 only: Prior exposure to E7080 or mTOR inhibitor
4) Subjects should not have received any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug and should have recovered from any toxicity related to previous anti-cancer treatment.
5) Major surgery within 3 weeks prior to the first dose of study drug
6) Subjects having > 1+ proteinuria on urinalysis will undergo 24-h urine collection for quantitative assessment of proteinuria. Subjects with urine protein = 1 g/24-hour will be ineligible.
7) Uncontrolled diabetes as defined by fasting serum glucose > 1.5 x ULN.
8) Fasting total cholesterol > 7.75 mmol/L (>300 mg/dl).
9) Fasting triglyceride level > 2.5 x ULN.
10) Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of E7080 or everolimus.
11) Significant cardiovascular impairment: history of congestive heart failure greater than New York heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment.
12) Prolongation of QTc interval to > 480 msec.
13) Bleeding disorder or thrombotic disorder requiring anticoagulant therapy, such as warfarin, or similar agents requiring therapeutic international normalized ratio (INR) monitoring (treatment with low molecular weight heparin [LMWH] is allowed).
14) Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.
15) Active infection (any infection requiring treatment).
16) Phase 2 only: Active malignancy (except for renal cell carcinoma, melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
17) Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (eg, sirolimus, everolimus, temsirolimus) or any of the excipients.
18) Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.
19) Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
20) Females who are pregnant or breastfeeding.
21) Medical need for the continued use of potent inhibitors of CYP3A4.

Study & Design

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