- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02501551
Regorafenib, C-kit Mutated Malignant Melanoma, 2nd Line Therapy
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 Overview
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Sang Joon Shin
- Phone Number: 02-2228-8138
Study Locations
-
-
-
Seoul, Korea, Republic of, 120-752
- Recruiting
- Severance Hospital, Yonsei University Health System
-
Contact:
- Sang Joon Shin
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Regorafenib
160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle
|
160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
disease control rate as measured by RECIST 1.1
Time Frame: at 8 weeks
|
at 8 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 4-2014-0573
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Melanoma
-
H. Lee Moffitt Cancer Center and Research InstituteTurnstone Biologics, Corp.RecruitingMetastatic Melanoma | Conjunctival Melanoma | Ocular Melanoma | Unresectable Melanoma | Uveal Melanoma | Cutaneous Melanoma | Mucosal Melanoma | Iris Melanoma | Acral Melanoma | Non-Cutaneous MelanomaUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Mucosal Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Ciliary Body and Choroid Melanoma, Small Size | Iris Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IA Melanoma | Stage IB Melanoma | Stage IIA MelanomaUnited States
-
Rutgers, The State University of New JerseyNational Cancer Institute (NCI); University of VirginiaCompletedStage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Stage III Skin Melanoma | Stage IIA Skin Melanoma | Stage IIB Skin Melanoma | Stage IIC Skin Melanoma | Stage IIIA Skin Melanoma | Stage IA Skin Melanoma | Stage IB Skin Melanoma | Stage 0 Skin Melanoma | Stage I Skin Melanoma | Stage II Skin MelanomaUnited States
-
MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Melanoma | Stage IV Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Stage IIB Melanoma | Stage IIC Melanoma | Stage IIA MelanomaUnited States
-
National Cancer Institute (NCI)CompletedStage IV Melanoma | Ciliary Body and Choroid Melanoma, Medium/Large Size | Iris Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIB Melanoma | Stage IIC MelanomaUnited States
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Melanoma | Stage IV Melanoma | Metastatic Intraocular Melanoma | Recurrent Intraocular Melanoma | Stage IV Intraocular Melanoma | Stage IIIA Melanoma | Stage IIIB Melanoma | Stage IIIC Melanoma | Extraocular Extension Melanoma | Stage IIIA Intraocular Melanoma | Stage IIIB Intraocular Melanoma | Stage...United States
-
Emory UniversityGenentech, Inc.Active, not recruitingStage IV Skin Melanoma | Stage IIIB Skin Melanoma | Stage IIIC Skin Melanoma | Unresectable Melanoma | Stage III Melanoma | Stage IIIA Skin Melanoma | Cutaneous Melanoma, Stage III | Cutaneous Melanoma, Stage IVUnited States
-
BiocadRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma Metastatic | Melanoma Unresectable | Melanoma AdvancedIndia, Russian Federation, Belarus
Clinical Trials on regorafenib
-
Second Affiliated Hospital of Guangzhou Medical...Cancer Institute and Hospital, Chinese Academy of Medical Sciences; Shenzhen... and other collaboratorsActive, not recruitingHepatocellular Carcinoma Non-resectableChina
-
Zhongda HospitalSun Yat-sen University; Jiangsu Cancer Institute & Hospital; Zhejiang University and other collaboratorsNot yet recruitingHepatocellular Carcinoma
-
Spanish Cooperative Group for the Treatment of...BayerCompletedColorectal Neoplasms | Metastatic DiseaseSpain
-
Rennes University HospitalRecruiting
-
Taipei Veterans General Hospital, TaiwanChang Gung Memorial Hospital; Koo Foundation Sun Yat-Sen Cancer CenterCompletedMetastatic Colorectal CancerTaiwan
-
Spanish Cooperative Group for the Treatment of...BayerCompletedStudy Comparing Different Dose Approaches of Induction Treatment of Regorafenib in MCRC (RE-ARRANGE)Metastatic Colorectal CancerSpain
-
Tianjin Medical University Cancer Institute and...Not yet recruitingAdvanced/Metastatic Colorectal CancerChina
-
Gustave Roussy, Cancer Campus, Grand ParisBayerRecruiting
-
Institute of Mother and Child, Warsaw, PolandMaria Sklodowska-Curie National Research Institute of OncologyRecruitingOsteosarcoma | Ewing Sarcoma of BonePoland
-
Massachusetts General HospitalBayerCompletedAcute Myeloid LeukemiaUnited States