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

NCT ID: NCT01136733

Last Updated: 2019-02-27

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

173 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-08-05

Study Completion Date

2018-02-08

Brief Summary

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

Detailed Description

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Conditions

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Metastatic Renal Cell Carcinoma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Lenvatinib

Group Type EXPERIMENTAL

Lenvatinib

Intervention Type DRUG

taken orally, once a day

Lenvatinib plus Everolimus

Group Type EXPERIMENTAL

Lenvatinib

Intervention Type DRUG

taken orally, once a day

Everolimus

Intervention Type DRUG

taken orally, once a day

Everolimus

Group Type ACTIVE_COMPARATOR

Everolimus

Intervention Type DRUG

taken orally, once a day

Interventions

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Lenvatinib

taken orally, once a day

Intervention Type DRUG

Everolimus

taken orally, once a day

Intervention Type DRUG

Other Intervention Names

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E7080, Lenvima, Kisplyx Afinitor

Eligibility Criteria

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Inclusion Criteria

* Histologically confirmed diagnosis of renal cell carcinoma.
* Phase 2: Histological or cytological confirmation of predominant clear cell renal cell carcinoma (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.

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 lenvatinib. Phase 2 only: Prior exposure to lenvatinib or mammalian target of rapamycin (mTOR) inhibitor.
* Subjects should not have received any anticancer 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 anticancer treatment. Major surgery within 3 weeks prior to the first dose of study drug.
* Subjects having greater than 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 hours will be ineligible. Uncontrolled diabetes as defined by fasting serum glucose at 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eisai Medical Services

Role: STUDY_DIRECTOR

Eisai Limited

Locations

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Tucson, Arizona, United States

Site Status

Orange, California, United States

Site Status

San Diego, California, United States

Site Status

Tampa, Florida, United States

Site Status

Joliet, Illinois, United States

Site Status

Louisville, Kentucky, United States

Site Status

Annapolis, Maryland, United States

Site Status

Bethesda, Maryland, United States

Site Status

Boston, Massachusetts, United States

Site Status

Tupelo, Mississippi, United States

Site Status

New York, New York, United States

Site Status

Tulsa, Oklahoma, United States

Site Status

Charleston, South Carolina, United States

Site Status

Dallas, Texas, United States

Site Status

Brno, , Czechia

Site Status

Olomouc, , Czechia

Site Status

Prague, , Czechia

Site Status

Gdansk, , Poland

Site Status

Lodz, , Poland

Site Status

Szczecin, , Poland

Site Status

Warsaw, , Poland

Site Status

Barcelona, , Spain

Site Status

Córdoba, , Spain

Site Status

Madrid, , Spain

Site Status

Pamplona, , Spain

Site Status

Bristol, , United Kingdom

Site Status

Cambridge, , United Kingdom

Site Status

Cardiff, , United Kingdom

Site Status

Glasgow, , United Kingdom

Site Status

Guildford, , United Kingdom

Site Status

Ipswich, , United Kingdom

Site Status

Leicester, , United Kingdom

Site Status

London, , United Kingdom

Site Status

Manchester, , United Kingdom

Site Status

Metropolitan Borough of Wirral, , United Kingdom

Site Status

Southampton, , United Kingdom

Site Status

Surrey, , United Kingdom

Site Status

Countries

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United States Czechia Poland Spain United Kingdom

References

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Lee CH, Motzer RJ, Glen H, Michaelson MD, Larkin J, Minoshima Y, Kanekiyo M, Ikezawa H, Sachdev P, Dutcus CE, Funahashi Y, Voss MH. Correlative serum biomarker analyses in the phase 2 trial of lenvatinib-plus-everolimus in patients with metastatic renal cell carcinoma. Br J Cancer. 2021 Jan;124(1):237-246. doi: 10.1038/s41416-020-01092-0. Epub 2020 Oct 7.

Reference Type DERIVED
PMID: 33024271 (View on PubMed)

Motzer RJ, Hutson TE, Glen H, Michaelson MD, Molina A, Eisen T, Jassem J, Zolnierek J, Maroto JP, Mellado B, Melichar B, Tomasek J, Kremer A, Kim HJ, Wood K, Dutcus C, Larkin J. Lenvatinib, everolimus, and the combination in patients with metastatic renal cell carcinoma: a randomised, phase 2, open-label, multicentre trial. Lancet Oncol. 2015 Nov;16(15):1473-1482. doi: 10.1016/S1470-2045(15)00290-9. Epub 2015 Oct 22.

Reference Type DERIVED
PMID: 26482279 (View on PubMed)

Other Identifiers

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E7080-G000-205

Identifier Type: -

Identifier Source: org_study_id

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