Clinical trial NCT01136967: An Open-Label, 2-Cohort, Multicenter, Study of Lenvatinib in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma
Official title: An Open-Label, 2-Cohort, Multicenter, Phase 2 Study of E7080 (Lenvatinib) in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Unresectable Stage III
Stage IV Melanoma
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2010-06-04
Enrollment: 182
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: This was a Phase 2, multicenter, open-label, 2-cohort, 2-stage study that assessed the ORR of lenvatinib in previously treated participants with AJCC unresectable Stage III or Stage IV melanoma and disease progression. Cohort 1 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, and is referred to as Cohort 1 or V600E BRAF negative. Other less common BRAF activating mutations were allowed as long as the participant did not receive a BRAF-targeted therapy. Cohort 2 enrolled participants harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF V600E-targeted therapy, and is referred to as Cohort 2 or V600E BRAF positive. Eligible participants had measurable disease according to RECIST 1.1.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed diagnosis of melanoma.
2. Unresectable Stage III or Stage IV melanoma.
3. Evidence of disease progression according to RECIST 1.1 on prior regimen.
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
6. Adequately controlled blood pressure.
7. Adequate renal function, bone marrow function, blood coagulation function, and liver function, as defined in the study protocol.

Exclusion Criteria:

1. Melanoma of intraocular origin.
2. 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.
3. 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).
4. Significant cardiovascular impairment.
5. Bleeding disorder or a thrombotic disorder requiring anticoagulant therapy.
6. Females who are pregnant or breastfeeding.
7. Prolongation of QTc interval to greater than 480 msec.
8. 24 hour urine protein greater than or equal to 1 gm.
9. Active hemoptysis within 3 wks prior to the first dose of study drug.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: 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:
measure: Progression Free Survival (PFS)
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Clinical Benefit Rate (CBR)
timeFrame: 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
measure: Number of Participants With Adverse Events (AEs)/ Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib
timeFrame: 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
measure: Change From Baseline in the Concentration of Clinical Biomarkers in Whole Blood
timeFrame: Cycle 1 Day 15 (C1 D15), Cycle 2 Day 1 (C2 D1), Cycle 3 Day 1 (C3 D1), Off-Treatment/Phase Visit 98 (V98)
measure: Summary of Plasma Concentration of Lenvatinib
timeFrame: Predose and 2 to 12 hours postdose at Cycle 1 Day 1 (C1D1), Cycle 1 Day 15 (C1D15), and Cycle 2 Day 1 (C2D1)
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Tucson
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state: Arizona
city: Los Angeles
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state: California
city: San Francisco
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state: California
city: Aurora
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state: Colorado
city: Boulder
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city: Colorado Springs
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city: Denver
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city: Lakewood
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state: Colorado
city: Littleton
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state: Colorado
city: Lone Tree
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state: Colorado
city: Longmont
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city: Parker
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state: Colorado
city: Thornton
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state: Colorado
city: Bonita Springs
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state: Florida
city: Bradenton
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state: Florida
city: Cape Coral
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city: Clearwater
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city: Englewood
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city: Fort Myers
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city: Naples
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city: North Port
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city: Orlando
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city: Palm Harbor
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city: Port Charlotte
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city: Sarasota
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state: Florida
city: Sebring
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state: Florida
city: Tampa
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city: Venice
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city: Louisville
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state: Kentucky
city: Boston
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state: Massachusetts
city: Detroit
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state: Michigan
city: Burnsville
country: United States
state: Minnesota
city: Coon Rapids
country: United States
state: Minnesota
city: Edina
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state: Minnesota
city: Fridley
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state: Minnesota
city: Maplewood
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state: Minnesota
city: Minneapolis
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state: Minnesota
city: Saint Paul
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state: Minnesota
city: Woodbury
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state: Minnesota
city: Southaven
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state: Mississippi
city: Saint Louis
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state: Missouri
city: Henderson
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state: Nevada
city: Las Vegas
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state: Nevada
city: Lebanon
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state: New Hampshire
city: Morristown
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
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state: Ohio
city: Eugene
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state: Oregon
city: Portland
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state: Oregon
city: Springfield
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state: Oregon
city: Tualatin
country: United States
state: Oregon
city: Bethlehem
country: United States
state: Pennsylvania
city: Philadelphia
country: United States
state: Pennsylvania
city: Bartlett
country: United States
state: Tennessee
city: Franklin
country: United States
state: Tennessee
city: Gallatin
country: United States
state: Tennessee
city: Germantown
country: United States
state: Tennessee
city: Hermitage
country: United States
state: Tennessee
city: Lebanon
country: United States
state: Tennessee
city: Memphis
country: United States
state: Tennessee
city: Murfreesboro
country: United States
state: Tennessee
city: Nashville
country: United States
state: Tennessee
city: Smyrna
country: United States
state: Tennessee
city: Bedford
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Grapevine
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Arlington
country: United States
state: Virginia
city: Fairfax
country: United States
state: Virginia
city: Gainesville
country: United States
state: Virginia
city: Leesburg
country: United States
state: Virginia
city: Winchester
country: United States
state: Virginia
city: Woodbridge
country: United States
state: Virginia
city: Vancouver
country: United States
state: Washington
city: Madison
country: United States
state: Wisconsin
city: Adelaide
country: Australia
city: Malvern
country: Australia
city: Newcastle
country: Australia
city: North Sydney
country: Australia
city: Perth
country: Australia
city: Westmead
country: Australia
city: Essen
country: Germany
city: Hannover
country: Germany
city: Heidelberg
country: Germany
city: Kiel
country: Germany
city: Mainz
country: Germany
city: Tubingen
country: Germany
city: Glasgow
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Surrey
country: United Kingdom
Study officials:
affiliation: Eisai Limited
name: Eisai US Medical Services
role: STUDY_DIRECTOR
References: