Ignite Creation Date:
2024-05-06 @ 7:15 AM
Last Modification Date:
2024-10-26 @ 11:46 AM
Study NCT ID:
NCT02501551
Status:
UNKNOWN
Last Update Posted:
2021-04-05
First Post:
2015-03-05
Brief Title:
Regorafenib C-kit Mutated Malignant Melanoma 2nd Line Therapy
Sponsor:
Yonsei University
Organization:
Yonsei University
Study Overview
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
Status:
UNKNOWN
Status Verified Date:
2021-04
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a phase II trial of regorafenib in patients with metastatic melanoma harboring c-Kit mutations andor 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 2011305222327-2334 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 2011292904-9 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
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 2011305222327-2334 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 2011292904-9 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None