MelanomaPhase 2NCT02501551
Regorafenib, C-kit Mutated Malignant Melanoma, 2nd Line Therapy
A Phase 2 study testing regorafenib in people with Melanoma, run by Yonsei University at 1 site in South Korea.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- regorafenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteSouth Korea
- Study dates
- Feb 2015to Jun 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Sang Joon Shin contact
South Korea1 site, 1 recruiting
- Recruiting
Severance Hospital, Yonsei University Health System
Seoul, 120-752
Sang Joon Shin
About this study
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
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).
Read the 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.
- Conditions
- Melanoma
- Being tested
- regorafenib
- Keywords
- Malignant melanoma, C-KIT mutation
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
regorafenibDrug
160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle
| Study group | Role | What they receive |
|---|---|---|
| Regorafenib | Experimental | 160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle Receives: Drug: regorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
disease control rate as measured by RECIST 1.1
Measured: at 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2015 (estimated)
- Study startFeb 2015
- Primary completionMay 2022 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MelanomaStudies of the same condition, open and under way.
- More trials run by Yonsei UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yonsei University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sang Joon Shin, Yonsei University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02501551
- Sponsor's protocol ID
- 4-2014-0573
- Status last verified
- Apr 2021
- First submitted
- 5 Mar 2015
- Last updated
- 5 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02501551
- Acronym / sponsor ID
- 4-2014-0573
- Conditions
- Melanoma
- Keywords
- Malignant melanoma, C-KIT mutation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Yonsei UniversityUniversity, hospital or other
- Study start
- Feb 2015
- Primary completion
- May 2022 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 17 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Regorafenib | Experimental | Drug: regorafenib160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| regorafenib160mg regorafenib once daily with a low fat breakfast for the first 21 days of each 28-day cycle | Drug | Regorafenib |
Primary outcome
disease control rate as measured by RECIST 1.1
Time frame: at 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sang Joon Shin contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing regorafenib in people with Melanoma, run by Yonsei University at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sang Joon Shin (02-2228-8138), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
disease control rate as measured by RECIST 1.1 (time frame: at 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2021.