A Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior Vascular Endothelial Growth Factor (VEGF)-Targeted Treatment - Full Text View

Sponsor:	Eisai Inc.
Information provided by (Responsible Party):	Eisai Inc.
ClinicalTrials.gov Identifier:	NCT01136733

Purpose

This is an open-label, multicenter, Phase 1b/2 study of E7080 alone and in combination with everolimus in subjects with unresectable advanced or metastatic renal cell carcinoma following one prior VEGF-targeted treatment.

Condition	Intervention	Phase
Metastatic Renal Cell Carcinoma	Drug: E7080 Drug: Everolimus Drug: E7080 plus Everolimus	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Open-Label, Multicenter, Phase 1b/2 Study of E7080 Alone, and in Combination With Everolimus in Subjects With Unresectable Advanced or Metastatic Renal Cell Carcinoma Following One Prior VEGF-Targeted Treatment

Resource links provided by NLM:

Drug Information available for: Sirolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Eisai Inc.:

Primary Outcome Measures:

Phase 1b=Dose-limiting toxicity (DLT) [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]
Phase 1b= Maximally tolerated dose (MTD [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]
Phase 1b= Recommended Phase 2 (RP2) dose [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]
Phase 2=Progression-free survival (PFS) [ Time Frame: first dose to first documentation of disease progression or death measured every 8 weeks, safety cycle 1 (days 1,8,15) subsequent cycles (days 1&15) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-Free Survival (PFS) [ Time Frame: Time is from Baseline to first evidence of disease progression.Assessments are performed every 2 months ] [ Designated as safety issue: No ]
Overall Survival (OS) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
Objective Response Rate (ORR) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
Disease Control Rate (DCR) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
Durable Stable Disease (SD) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
The portion of subjects whose best over all response is SD and the the duration of of SD > 23 weeks.
Clinical Benefit Rate (CBR) [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
Pharmacokinetic (PK) and pharmacodynamic (PD) profile. [ Time Frame: Time is from Baseline to first evidence of disease progression. Assessments are performed every 2 months ] [ Designated as safety issue: No ]
Plasma concentrations of E7080 and whole blood concentrations of everolimus at Cycle 1 days 1 and 15, Cycle 2 day 1 Cycle 3 Day 1

Estimated Enrollment:	180
Study Start Date:	August 2010
Estimated Primary Completion Date:	September 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: E7080	Drug: E7080 taken orally,once a day
Experimental: E7080 plus Everolimus	Drug: E7080 plus Everolimus orally once a day
Active Comparator: Everolimus	Drug: Everolimus orally once a day

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Select Inclusion Criteria:

Histologically confirmed diagnosis of renal cell carcinoma.
Phase 2: Histological or cytological confirmation of predominant clear cell RCC (original tissue diagnosis of RCC is acceptable).
Documented evidence of unresectable advanced or metastatic RCC. Phase 2: Radiographic evidence of disease progression according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
Phase 2: One prior 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.
Phase 2: Measurable disease meeting the following criteria: a.) at least 1 lesion of greater than or equal to 1.5 cm in the longest diameter for a non-lymph node or greater than or equal to 1.5 cm in the short axis diameter for a lymph node which is serially measurable according to Modified RECIST 1.1 using computerized tomography/magnetic resonance imaging (CT/MRI) or photography. Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP less than or equal to 150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Screening Visit.

Select Exclusion Criteria:

Phase 1b or Phase 2 specific per below:

Phase 1b only: Subjects with untreated or unstable metastasis to the central nervous system (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 (e.g., brain or leptomeningeal) metastasis are excluded.
Phase 2 only: More than one prior VEGF-targeted treatment for unresectable advanced or metastatic RCC.

Phase 1b or Phase 2 specific per below:

Phase 1b only: Prior exposure to E7080. Phase 2 only: Prior exposure to E7080 or mammalian target of rapamycin (mTOR) inhibitor.
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. Major surgery within 3 weeks prior to the first dose of study drug.
Subjects having > 1+ proteinuria on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria.
Subjects with urine protein greater than or equal to 1 g/24-hour will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose >1.5 X ULN.
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.
Known intolerance to any of the study drugs (or any of the excipients) and/or known hypersensitivity to rapamycins (e.g., sirolimus, everolimus, temsirolimus) or any of the excipients.
Phase 1b only: Subjects who discontinued prior tyrosine kinase inhibitor due to toxicity will be ineligible.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136733

Contacts

Contact: Eisai Inc. Eisai Medical Services

1-888-422-4743

Locations

United States, Maryland
	Recruiting
Bethesda, Maryland, United States
United States, Massachusetts
	Recruiting
Boston, Massachusetts, United States
Contact: Eisai Medical Services
United States, Mississippi
	Recruiting
Tupelo, Mississippi, United States
United States, New York
	Recruiting
New York, New York, United States
Contact: Eisai Medical Services
United States, Texas
	Recruiting
Dallas, Texas, United States
United Kingdom
	Recruiting
London, United Kingdom
	Recruiting
Surrey, United Kingdom
Contact: EU Medical Service +442075387075

Sponsors and Collaborators

Eisai Inc.

Investigators

Study Director:

Eisai Medical Services

Eisai Limited

More Information

No publications provided

Responsible Party:	Eisai Inc.
ClinicalTrials.gov Identifier:	NCT01136733 History of Changes
Other Study ID Numbers:	E7080-G000-205
Study First Received:	May 26, 2010
Last Updated:	April 4, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eisai Inc.:

Unresectable advanced or metastatic renal cell carcinoma

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Everolimus

Sirolimus
Endothelial Growth Factors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Antifungal Agents
Anti-Infective Agents
Anti-Bacterial Agents
Growth Substances

ClinicalTrials.gov processed this record on May 23, 2012