Regorafenib, C-kit Mutated Malignant Melanoma, 2nd Line Therapy
Primary Purpose
Melanoma
Status
Unknown status
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
regorafenib
Sponsored by
About this trial
This is an interventional treatment trial for Melanoma focused on measuring Malignant melanoma, C-KIT mutation
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically proven melanoma with stage IV or unresectable stage III disease
- c-kit mutations
- performance status of 0, 1, and 2
- Have progressed after 1 previous systemic treatment containing dacarbazine, temozolomide, or immunotherapy for metastatic melanoma
- Patients with central nervous system metastasis must have stable neurologic function without evidence of central nervous system progression within 8 weeks
- Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors v1.1
Exclusion Criteria:
- Major surgery or radiation therapy within 4 weeks of starting the study treatment
- History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease
- Have received greater than or equal to 2 previous chemotherapy-containing systemic treatment regimens
- Patients with BRAF or NRAS mutation
- Prior therapy with a c-kit inhibitor
- Significant history of cardiac disease, myocardial infarction, or current cardiac ventricular arrhythmias requiring medication
- Major surgery within 4 weeks before start of study treatment
- Active gastrointestinal bleeding
- Patients treated with co-administration of a strong CYP3A4 inducers
- Adequate Hematologic, Biochemical, and Organ Function
Sites / Locations
- Severance Hospital, Yonsei University Health SystemRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Regorafenib
Arm Description
160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle
Outcomes
Primary Outcome Measures
disease control rate as measured by RECIST 1.1
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02501551
Brief Title
Regorafenib, C-kit Mutated Malignant Melanoma, 2nd Line Therapy
Official Title
A Phase II Study to Evaluate the Efficacy of Regorafenib in C-kit Mutated Metastatic Malignant Melanoma Failed First-Line Dacarbazine, Temozolomide or Immune Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Unknown status
Study Start Date
February 2015 (undefined)
Primary Completion Date
May 2022 (Anticipated)
Study Completion Date
June 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Yonsei University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a phase II trial of regorafenib in patients with metastatic melanoma harboring c-Kit mutations and/or amplifications of c-Kit gene copy number. The primary end point is disease control rate (DCR), and the secondary end points are safety, response rate (RR), progression free survival (PFS), and overall survival (OS).
Detailed Description
The incidence of melanoma is rising globally and mortality is increasing faster than most other cancers. Recent advances in the molecular biology of melanoma have uncovered several potential therapeutic targets in melanoma. It has been observed that 81% of melanomas arising from non-chronic sun-damaged skin have an oncogenic BRAF or NRAS mutation, whereas such mutations are far less frequent in chronic sun-damaged skin melanomas, acral melanomas, or mucosal melanomas. In contrast, c-Kit mutations are more common in mucosal and acral melanomas, which can also be accompanied by an increase in c-Kit copy numbers.
Asian populations, the most common melanoma subtypes are acral and mucosal melanoma, which comprise greater than 70% of all melanomas, a rate that is much higher than that seen in white populations (6% to 7%). KIT mutations or amplification are reported about 20% in acral or mucosal melanomas (JAMA. 2011;305(22):2327-2334). Therefore, c-Kit mutations are likely the most common kind of genetic mutations in Asians, and the investigation of c-Kit inhibitors is a high priority in this population.
Imatinib mesylate (Gleevec, formerly STI571; Novartis Pharmaceuticals, Basel, Switzerland), is a selective inhibitor, targeting Abl as well as c-Kit and the platelet-derived growth factor receptor. Imatinib demonstrated significant activity in patients with metastatic melanoma harboring genetic c-Kit aberrations, with an overall response rate of 29% (J Clin Oncol 2011;29:2904-9) Regorafenib (BAY 73-4506) is a novel, orally active, diphenylurea multikinase inhibitor of VEGFR1-3, c-KIT, TIE-2, PDGFR-β, FGFR-1, RET, RAF-1, BRAF and p38 MAP kinase. Regorafenib provide a significant improved PFS and OS in patients with GIST and colorectal cancer, respectively (Lancet 2013; 381: 295-302, Lancet 2013; 381: 303-12). Especially, inhibitory activity of regorafenib is most effective in c-kit mutated tumors. Therefore, regorafenib has a chance to significant activity in melanoma with c-kit mutations. However, no clinical trials have been published for regorafenib in the patients with melanoma who harbor c-Kit mutations.
NCCN recommend ipilimumab, high-dose interleukin-2, and vemurafenib or dabrafenib for BRAF mutated tumor as a preferred regimen, and imatinib for c-kit mutated tumors, dacarbazine, temozolomide, and paclitaxel as other active regimens. In Korea, ipilimumab is not available yet and imatinib for c-kit mutated tumors is not used legally. Thus, regorafenib could be used for c-kit mutated tumor in clinical trial setting.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma
Keywords
Malignant melanoma, C-KIT mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Regorafenib
Arm Type
Experimental
Arm Description
160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle
Intervention Type
Drug
Intervention Name(s)
regorafenib
Intervention Description
160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle
Primary Outcome Measure Information:
Title
disease control rate as measured by RECIST 1.1
Time Frame
at 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically proven melanoma with stage IV or unresectable stage III disease
c-kit mutations
performance status of 0, 1, and 2
Have progressed after 1 previous systemic treatment containing dacarbazine, temozolomide, or immunotherapy for metastatic melanoma
Patients with central nervous system metastasis must have stable neurologic function without evidence of central nervous system progression within 8 weeks
Measurable disease or non-measurable but evaluable disease, according to the Response Evaluation Criteria in Solid Tumors v1.1
Exclusion Criteria:
Major surgery or radiation therapy within 4 weeks of starting the study treatment
History of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease
Have received greater than or equal to 2 previous chemotherapy-containing systemic treatment regimens
Patients with BRAF or NRAS mutation
Prior therapy with a c-kit inhibitor
Significant history of cardiac disease, myocardial infarction, or current cardiac ventricular arrhythmias requiring medication
Major surgery within 4 weeks before start of study treatment
Active gastrointestinal bleeding
Patients treated with co-administration of a strong CYP3A4 inducers
Adequate Hematologic, Biochemical, and Organ Function
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sang Joon Shin
Phone
02-2228-8138
Facility Information:
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
120-752
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sang Joon Shin
12. IPD Sharing Statement
Learn more about this trial
Regorafenib, C-kit Mutated Malignant Melanoma, 2nd Line Therapy
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