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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01136967
First received: June 2, 2010
Last updated: February 16, 2016
Last verified: February 2016
  Purpose
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.

Condition Intervention Phase
Unresectable Stage III
Stage IV Melanoma
Drug: Lenvatinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Objective Response Rate (ORR) [ Time Frame: From date of first dose of study drug until all participants completed a minimum of 6 cycles (28-day cycles) or discontinued treatment prior to end of Cycle 6 by the date of data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively) ] [ Designated as safety issue: No ]
    ORR 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 and assessed by magnetic resonance imaging/computed tomography (MRI/CT) scans, as determined by 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 CR or PR assessment at least 4 weeks later. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 millimeters. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.


Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years ] [ Designated as safety issue: No ]
    PFS was measured as the time from the date of first administration of study treatment until the date of first documentation of disease progression or date of death from any cause (whichever occurred first), as determined by IRR and Investigator based on RECIST v1.1. Disease progression per RECIST v1.1 was defined as at least a 20% relative increase and 5 mm absolute increase in the sum of diameters of target lesions (taking as reference the smallest sum on study) recorded since the treatment started or the appearance of 1 or more new lesions.

  • Overall Survival (OS) [ Time Frame: From date of first dose of study drug until date of death from any cause or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years ] [ Designated as safety issue: No ]
    OS was defined as the length of time in months from the date of first administration of study drug until the date of death from any cause, and was based on the data cutoff date for each cohort.

  • Disease Control Rate (DCR) [ Time Frame: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years ] [ Designated as safety issue: No ]
    DCR was defined as the percentage of participants who had a BOR of CR or PR or stable disease (SD). To be assigned a BOR of SD, the time from the first administration of study drug until the date of documented SD needed to be greater than or equal to seven weeks based on IRR and Investigator's assessment. DCR = CR + PR + SD

  • Clinical Benefit Rate (CBR) [ Time Frame: From date of first dose of study drug until documentation of disease progression or death from any cause (whichever occurred first) or up to data cutoff (Jan 2012 and Apr 2013 for Cohort 1 and Cohort 2, respectively), up to approximately 2.9 years ] [ Designated as safety issue: No ]
    CBR was defined as the percentage of participants who had a BOR of CR or PR or durable SD (SD lasting greater than or equal to 23 weeks) based on IRR and Investigator's assessment. CBR = CR + PR + durable SD rate

  • Number of Participants With Adverse Events (AEs)/ Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability of Lenvatinib [ Time Frame: For each participant, from the first patient first dose till 30 days after the last dose of study drug, up to approximately 2.9 years ] [ Designated as safety issue: Yes ]
    Safety was assessed by monitoring and recording all AEs including all Common Terminology Criteria for Adverse Events (CTCAE) grades and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, electrocardiograms (ECGs), and multi-gated acquisition (MUGA) scans or echocardiogram.

  • Pharmacokinetics and Pharmacodynamics [ Time Frame: Predose and 2 to 12 hours postdose at Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1 ] [ Designated as safety issue: No ]
    Due to the sparse PK sampling in this study, the data were pooled with data from other Phase 1 studies conducted in participants with solid tumors.


Enrollment: 182
Study Start Date: August 2010
Study Completion Date: November 2014
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (V600E BRAF negative)
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
Participants received lenvatinib 24 mg orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.
Other Name: E7080
Experimental: Cohort 2 (V600E BRAF positive)
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
Participants received lenvatinib 24 mg orally, once daily continuously in 28-day cycles until disease progression, development of unacceptable toxicity or withdrawal of consent.
Other Name: E7080

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

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136967

  Show 95 Study Locations
Sponsors and Collaborators
Eisai Inc.
Investigators
Study Director: Eisai US Medical Services Eisai Limited
  More Information

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01136967     History of Changes
Other Study ID Numbers: E7080-G000-206 
Study First Received: June 2, 2010
Results First Received: March 13, 2015
Last Updated: February 16, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Lenvatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 28, 2016