An Open-Label, 2-Cohort, Multicenter, Study of Lenvatinib in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma

NCT01136967 | Completed Phase 2 Results

• 1 other identifier: E7080-G000-206
• Study Type: interventional
• Target: 182
• Locations: 4 countries
• Sites: 95

Brief Summary

The purpose of this study is to assess the objective response rate of lenvatinib in previously treated participants with American Joint Committee on Cancer (AJCC) unresectable Stage III or Stage IV melanoma and disease progression.

Conditions

Unresectable Stage III; Stage IV Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR, (ORR = CR + PR) was defined as the percentage of participants in each cohort who had a best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 for target lesions assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans and independent radiologic review (IRR). A BOR of CR required confirmation by a subsequent CR assessment at least 4 weeks later. A BOR of PR required confirmation by a subsequent assessment of CR or PR at least 4 weeks later. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (target or non-target) had to have a reduction in short axis to less than (\<)10 mm. PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  From date of treatment start until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to end of Cycle 6 (up to 24 weeks)

Secondary Outcomes (7)

• Progression Free Survival (PFS)

  From date of treatment start until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months

• Overall Survival (OS)

  From date of treatment start until date of death from any cause or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months

• Disease Control Rate (DCR)

  From date of treatment start until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months

• Clinical Benefit Rate (CBR)

  From date of treatment start until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 8 months

• Number of Participants With Adverse Events (AEs)/ Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib

  From date of treatment start up to 30 days after the last dose, or up to data cutoff (Cohort 1; 15 Jan 2012 and Cohort 2; 15 Apr 2013), up to approximately 2 years 9 months

Study Arms (2)

Cohort 1 (V600E BRAF negative)

EXPERIMENTAL

Cohort 1 (V600E BRAF negative) enrolled participants not harboring the V600E BRAF mutation with disease progression following up to 2 prior systemic anticancer regimens (excluding anti-VEGF) for unresectable Stage III or Stage IV melanoma.

Drug: Lenvatinib

Cohort 2 (V600E BRAF positive)

EXPERIMENTAL

Cohort 2 (V600E BRAF positive) enrolled participants harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF V600E-targeted therapy.

Drug: Lenvatinib

Interventions

Lenvatinib DRUG

Participants received lenvatinib 24 mg orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.

Also known as: E7080

Cohort 1 (V600E BRAF negative); Cohort 2 (V600E BRAF positive)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed diagnosis of melanoma.
• Unresectable Stage III or Stage IV melanoma.
• Evidence of disease progression according to RECIST 1.1 on prior regimen.
• Participants with brain metastases will be eligible if they have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of disease recurrence in the brain or have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of disease progression in the brain; and are asymptomatic, and discontinued corticosteroid treatment at least 30 days prior starting treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequately controlled blood pressure.
• Adequate renal function, bone marrow function, blood coagulation function, and liver function, as defined in the study protocol.

You may not qualify if:

• Melanoma of intraocular origin.
• Leptomeningeal metastases or brain metastases except as for participants with brain metastases will be eligible if they have undergone complete surgical excision and are more then 1 month post surgery with no radiographic evidence of disease recurrence in the brain or have undergone stereotactic radio surgery (gamma knife procedure) and are more then 1 month post procedure and with no radiographic evidence of disease progression in the brain; and are asymptomatic, and discontinued corticosteroid treatment at least 30 days prior starting treatment.
• More than 2 prior systemic anticancer regimen treatments including immunotherapies for unresectable Stage III or Stage IV disease (if BRAF V600E mutation negative) or not previously treated with BRAF V600E-targeted therapy or received in the past more than 2 prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive).
• Significant cardiovascular impairment.
• Bleeding disorder or a thrombotic disorder requiring anticoagulant therapy.
• Females who are pregnant or breastfeeding.
• Prolongation of QTc interval to greater than 480 msec.
• hour urine protein greater than or equal to 1 gm.
• Active hemoptysis within 3 wks prior to the first dose of study drug.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (95)

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Birmingham, Alabama, United States

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Tucson, Arizona, United States

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Los Angeles, California, United States

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San Francisco, California, United States

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Aurora, Colorado, United States

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Boulder, Colorado, United States

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Colorado Springs, Colorado, United States

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Denver, Colorado, United States

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Lakewood, Colorado, United States

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Littleton, Colorado, United States

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Lone Tree, Colorado, United States

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Longmont, Colorado, United States

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Parker, Colorado, United States

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Thornton, Colorado, United States

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Bonita Springs, Florida, United States

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Bradenton, Florida, United States

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Cape Coral, Florida, United States

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Clearwater, Florida, United States

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Englewood, Florida, United States

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Fort Myers, Florida, United States

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Gainesville, Florida, United States

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Naples, Florida, United States

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North Port, Florida, United States

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Orlando, Florida, United States

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Palm Harbor, Florida, United States

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Port Charlotte, Florida, United States

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Sarasota, Florida, United States

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Sebring, Florida, United States

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Tampa, Florida, United States

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Venice, Florida, United States

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Louisville, Kentucky, United States

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Boston, Massachusetts, United States

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Detroit, Michigan, United States

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Burnsville, Minnesota, United States

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Coon Rapids, Minnesota, United States

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Edina, Minnesota, United States

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Fridley, Minnesota, United States

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Maplewood, Minnesota, United States

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Minneapolis, Minnesota, United States

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Saint Paul, Minnesota, United States

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Woodbury, Minnesota, United States

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Southaven, Mississippi, United States

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St Louis, Missouri, United States

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Henderson, Nevada, United States

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Las Vegas, Nevada, United States

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Lebanon, New Hampshire, United States

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Morristown, New Jersey, United States

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New York, New York, United States

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Cincinnati, Ohio, United States

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Cleveland, Ohio, United States

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Columbus, Ohio, United States

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Eugene, Oregon, United States

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Portland, Oregon, United States

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Springfield, Oregon, United States

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Tualatin, Oregon, United States

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Bethlehem, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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Bartlett, Tennessee, United States

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Franklin, Tennessee, United States

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Gallatin, Tennessee, United States

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Germantown, Tennessee, United States

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Hermitage, Tennessee, United States

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Lebanon, Tennessee, United States

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Memphis, Tennessee, United States

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Murfreesboro, Tennessee, United States

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Nashville, Tennessee, United States

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Smyrna, Tennessee, United States

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Bedford, Texas, United States

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Dallas, Texas, United States

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Grapevine, Texas, United States

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Houston, Texas, United States

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Arlington, Virginia, United States

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Fairfax, Virginia, United States

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Gainesville, Virginia, United States

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Leesburg, Virginia, United States

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Winchester, Virginia, United States

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Woodbridge, Virginia, United States

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Vancouver, Washington, United States

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Madison, Wisconsin, United States

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Adelaide, Australia

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Malvern, Australia

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Newcastle, Australia

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North Sydney, Australia

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Perth, Australia

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Westmead, Australia

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Essen, Germany

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Hanover, Germany

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Heidelberg, Germany

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Kiel, Germany

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Mainz, Germany

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Tübingen, Germany

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Glasgow, United Kingdom

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London, United Kingdom

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Nottingham, United Kingdom

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Surrey, United Kingdom

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MeSH Terms

Conditions

Melanoma

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Eisai Medical Services
• Organization: Eisai, Inc.

esi_medinfo@eisai.com

1-888-422-4743

Study Officials

• Eisai US Medical Services

  Eisai Limited

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 2, 2010
• First Posted: June 4, 2010
• Study Start: August 1, 2010
• Primary Completion: April 1, 2013
• Study Completion: November 1, 2014
• Last Updated: November 13, 2019
• Results First Posted: March 16, 2016

Record last verified: 2016-11

Locations

US (79); AU (6); DE (6); GB (4)