An Open-Label, 2-Cohort, Multicenter, Study of E7080 in Previously Treated Subjects With Unresectable Stage III or Stage IV Melanoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT01136967
First received: June 2, 2010
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to assess the objective response rate of E7080 in previously treated subjects with American Joint Committee on Cancer (AJCC) unresectable stage III or stage IV melanoma and disease progression. This study is currently recruiting participants only for Cohort 2. Enrollment is closed for cohort 1.


Condition Intervention Phase
Unresectable Stage III
Stage IV Melanoma
Drug: E7080
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 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 [ Time Frame: First dose -first documentation of disease progression or death measured every 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease Control Rate [ Time Frame: First Dose to disease progression or death followed every 8 weeks ] [ Designated as safety issue: No ]
  • Progression Free Survival [ Time Frame: First Dose to disease progression or death followed every 8 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: : First Dose to disease progression or death followed every 8 weeks ] [ Designated as safety issue: Yes ]
    First dose to disease progression or death followed every 8 weeks; Safety: Cycle 1 and 2 (Days 1,15), Cycles "X" , (Days 1); Overall survival - Follow-up every 4 to 8 weeks during the Treatment Phase then every 3 months for the first 2 years, then every 6 months during years 3 and 4 and yearly thereafter.

  • Pharmacokinetics and pharmacodynamics [ Time Frame: First Dose to disease progression or death followed every 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 182
Study Start Date: June 2010
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Drug: E7080
Given orally and once daily to subjects with negative BRAF-V600E mutation (other uncommon BRAF activation mutations are allowed) and not treated with BRAF targeted therapy.
Experimental: Cohort 2 Drug: E7080
Given orally and once daily to subjects with positive BRAF-V600E mutation (additional other uncommon activating BRAF mutations are allowed) and treated with BRAF-V600E targeted therapy

Detailed Description:

This is a multicenter, open-label, 2-cohort, 2 - stage, Phase 2 study to assess the objective response rate of E7080 in previously treated subjects with American Joint Committee on Cancer (AJCC) unresectable stage III or stage IV melanoma and disease progression. Cohort 1 will enroll subjects not harboring the V600E BRAF mutation with disease progression following up to two prior systemic anticancer regimen treatments for unresectable stage III or stage IV melanoma, Cohort 2 will enroll subjects harboring the activating BRAF mutations (mainly the V600E mutation) with disease progression following BRAF-V600E-targeted therapy. Eligible subjects must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  Eligibility

Ages Eligible for Study:   18 Years and older
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. Subjects 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
  8. Adequate bone marrow function
  9. Adequate blood coagulation function
  10. Adequate liver function
  11. Males or females greater than or equal to 18 years of age at the time of informed consent.
  12. Negative serum or urine pregnancy test
  13. Voluntary agreement to provide written informed consent

Exclusion Criteria:

  1. Melanoma of intraocular origin
  2. Leptomeningeal metastases or brain metastases except as for subjects 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 two prior systemic anticancer regimen treatments, including immunotherapies, in addition to a BRAF-V600E-targeted therapy (if BRAF V600E mutation positive)
  4. Any anti-cancer treatment within 21 days or any investigational agent within 30 days prior to the first dose of study drug
  5. Inability to take oral medication, gastrointestinal malabsorption, or any other condition that might affect the absorption of E7080.
  6. Major surgery within 3 weeks prior to the first dose of study drug.
  7. Significant cardiovascular impairment
  8. Bleeding disorder or a thrombotic disorder requiring anticoagulant therapy
  9. Active malignancy (except for melanoma, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months.
  10. Females who are pregnant or breastfeeding.
  11. Known intolerance to the study drug (or any of the excipients).
  12. Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial.
  13. prolongation of QTc interval greater than 480 msec 14.24 hour urine protein greater than or equal 1 gm

15.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

No publications provided

Responsible Party: Eisai Inc.
ClinicalTrials.gov Identifier: NCT01136967     History of Changes
Other Study ID Numbers: E7080-G000-206
Study First Received: June 2, 2010
Last Updated: April 1, 2014
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

ClinicalTrials.gov processed this record on July 24, 2014