AzTrials
AzTrials

Melanoma Stage IIIPhase 2RegoMelNCT05370807

A Clinical Trial of Regorafenib in Patients With Pretreated Advanced Melanoma

A Phase 2 study testing Regorafenib 40 MG Oral Tablet and Triplet therapy in people with Melanoma Stage III and Melanoma Stage IV, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

There are in total 3 cohorts. Cohort A: 16 patients will receive a daily dose of 80mg regorafenib up until progressive disease, unacceptable toxicity or withdrawal of consent. Dose can be escalated intra-patient up to 120 mg if no AE with a grad >1 at 28 days. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma Stage III, Melanoma Stage IV
What is being tested?
Regorafenib 40 MG Oral Tablet and Triplet therapy
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
48 participants
Where
1 siteBelgium
Study dates
3 Oct 2022to Mar 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • ≥ 18 years of age.
  • Signed written informed consent.
  • Histologically confirmed advanced melanoma that is either stage III (unresectable) or stage IV (metastatic, unresectable)
  • Subjects must have failed prior systemic treatment with immune checkpoint inhibitors, including CTLA-4 blocking immune checkpoint inhibitors (ipilimumab or other experimental anti-CTLA-4 antibodies), and PD-1 blocking immune checkpoint inhibitors (pembrolizumab, nivolumab or other experimental anti-PD-1 antibodies). Progression of disease per RECIST, version 1.1 (Eisenhauer et al. Eur J Cancer 2009) or per immune related response criteria (Wolchok et al, Clin Cancer Res 2009) must have been documented during this prior treatment. Patients with BRAFV600mutant melanoma must have failed treatment with a BRAF-(+/-MEK) inhibitor. Patients who are not able to undergo such treatment will be considered eligible if all other eligibility criteria are fulfilled.
  • The presence of at least one measurable lesion per RECIST, version 1.1 (Eisenhauer et al. Eur J Cancer 2009)
  • Interval between the date of the last administration of prior therapy for melanoma and the date of recruitment:
Show all 19Show fewer
  • ≥ 12 weeks following the date of the first administration and ≥ 3 weeks following the date of the last administration of an anti-CTLA-4-, PD-1- or PD-L1 blocking immune checkpoint inhibitor;
  • ≥ 4 weeks following the date of the last administration of chemotherapy (≥ 6 weeks in case of a nitrosurea or mitomycin C containing regimen);
  • Cohort-C: ≥ 12 weeks following the date of the last administration of BRAF-/MEK-inhibitors.
  • All prior anti-cancer treatment-related toxicities (except alopecia and laboratory values as listed on Table 1) and non-medical treatments (e.g. surgery and radiation therapy) must be ≤ Grade 1 severity according to the Common Terminology Criteria for Adverse Events version 5 (CTCAE version 5.0; National Cancer Institute (NCI) 2017) at the time of enrollment.
  • The patient must be able to swallow and retain oral medication and must not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
  • Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to recruitment and agree to use effective contraception throughout the treatment period, and for 16 weeks after the last dose of study treatment.
  • Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception from 14 days prior to administration of the first dose of study treatment, throughout the treatment period, and for 16 weeks after the last dose of study treatment.
  • An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Oken et al, Am J Clin Oncol 1982).
  • Adequate baseline organ function as defined in Table 1.
  • Negative proteinuria on dipstick or 24 hours proteinuria <1000mg.
  • Cohort-B and -C: the melanoma must carry a documented BRAFV600 mutation.
  • Cohort-B: patients should be on treatment with BRAF-/MEK-inhibitors or have interrupted for less than 4 weeks before initiation of the study treatment.
  • Cohort-C: patients should be off BRAF-/MEK-inhibitors for at least 12 weeks before initiation of the study treatment.

Who cannot join

  • 14. Subjects with uveal melanoma. 15. Subjects with clinically active brain metastases (lesions should be stable and have been definitely treated with stereotactic radiation therapy, surgery or gamma knife therapy with no evidence of disease progression prior to enrollment).
  • 16. Any contra-indication for evaluation by whole body 18F-FDG-PET/CT or MRI of the brain.
  • 17. History of another malignancy. Exception: subjects who have been disease-free for 3 years, (i.e. subjects with second malignancies that are indolent or definitively treated at least 3 years ago) or subjects with a history of completely resected non-melanoma skin cancer.
  • 18. Current use of any prohibited medication. 19. Taken an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to recruitment.
  • 20. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures.
  • 21. Known Human Immunodeficiency Virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Exception: subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.
Show all 20Show fewer
  • 22. Ongoing infection CTCAE v5.0 Grade > 2 requiring systemic therapy. 23. No enzyme inducing anticonvulsants for ≥ 4 weeks prior to recruitment 24. A history or evidence of cardiovascular risk including any of the following:
  • Current LVEF < LLN
  • A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec;
  • A history or evidence of current clinically significant uncontrolled arrhythmias. Exception: subjects with atrial fibrillation controlled for > 30 days prior to recruitment are eligible.
  • A history (within 6 months prior to recruitment) of acute coronary syndromes (including myocardial infarction or unstable angina), or coronary angioplasty;
  • History of deep venous or arterial thrombosis, or CVA the last 6 months
  • A history or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;
  • Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by antihypertensive therapy;
  • Patients with intra-cardiac defibrillators or permanent pacemakers;
  • Abnormal cardiac valve morphology (≥ grade 2; moderate valvular thickening) documented by echocardiogram (subjects with grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study).
  • 25. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
  • 26. Female patients who are nursing. Prior/Concomitant therapy 27. Prior treatment with regorafenib. 28. Cohort-B: 28.1. Patients treated with vemurafenib/cobimetinib 28.2. Patients who are unable to initiate regorafenib within 4 weeks after interruption BRAF-
  • /MEK-inhibitor therapy 29. Cohort-C: 29.1. Patients who have not interrupted BRAF-/MEK-inhibitor therapy for at least 12 weeks prior to initiation of study treatment. 30. Patients who received prior radiotherapy within 2 weeks of start of study treatment or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities. A 1-week washout is permitted for palliative radiation (duration of ≤2 weeks of radiotherapy) 31. Patients who have received a live vaccine or live attenuated replication competent vaccine within 32 days prior to the first dose of study treatment. Administration of non-live vaccines are allowed.
  • 33. Prior transplantation of human cells, tissues and organs (e.g. liver transplant) or candidates for any type of transplantation. 34. Patients on concomitant use of CYP3A4 inducers, strong CYP3A4 inhibitors and strong UGT1A9 inhibitors (e.g. mefenamic acid, diflunisal, and niflumic acid) within 2 weeks prior to start of study treatment. Prior/Concurrent Clinical Study Experience 35. Previous administration of an investigational drug within 28 days, or 5 half-lives (minimum 14 days) before the start of study treatment, whichever is shorter) or concomitant participation in another clinical study with investigational medicinal product(s). Other Exclusions 36. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator. 37. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the subject's safety, obtaining informed consent, or compliance with study procedures. 38. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. 39. Current use of any prohibited medication. 40. Any contra-indication for evaluation by whole body 18F-FDG-PET/CT and/or MRI of the brain

Trial locations and contacts

1 site in 1 country.

Belgium1 site

  • UZ Brussels

    Jette, Brussels Capital, 1090

Other trials in Belgium

About this study

Official title: A Phase-2 Clinical Trial of Regorafenib in Patients With Pretreated Advanced Melanoma - Definition of Two Additional Stratified Patient Cohorts of Regorafenib Plus BRAF-/MEK-inhibitors in Pretreated BRAF V600-mutant Melanoma Patients

There are in total 3 cohorts. Cohort A: 16 patients will receive a daily dose of 80mg regorafenib up until progressive disease, unacceptable toxicity or withdrawal of consent. Dose can be escalated intra-patient up to 120 mg if no AE with a grad >1 at 28 days. Patients get a baseline evaluation and have a consultation every 2 weeks for evaluation during treatment. This evaluation consists out of lab tests, PET/CT (not bi-weekly), MRI (not bi-weekly) and physical evaluation.

Primary endpoint is the anti-tumor activity, secondary endpoints are the Overall Survival Rate, Progression Free Survival and the incidence and severity of AE and Health-Related Quality of Life.

Read more

Cohort-B: 16 patients who are being treated with BRAF-/MEK- inhibitors will receive additional daily regorafenib in combination with BRAF-/MEK inhibitors. Approved BRAF-/MEK- inhibitor combinations include dabrafenib/trametinib and encorafenib/binimetinib. An interruption of BRAF-/MEK-inhibitors dosing of maximum 4 weeks is allowed between the documentation of progression of disease on this therapy and the initiation of regorafenib study treatment. Dose of regorafenib is 40mg.

Cohort-C: 16 patients in Cohort-C will have interrupted treatment with any BRAF- /MEK - inhibitor combination for at least 12 weeks prior to initiating study therapy with regorafenib. At the time of initiating regorafenib study treatment at 40mg, patients will also resume treatment with encorafenib/binimetinib at its standard dosing regimen.

The first 6 patients enrolled in each Cohort (B, and -C) will be considered as a safety lead-in study population. If two or more serious treatment-related adverse events are observed among the first 6 patients, enrollment will be suspended (if applicable).

The risk/benefit for continuing enrollment will be evaluated and an interim safety report will be provided to the Medical Ethics Committee of the UZ Brussel. If less than two serious treatment-related adverse events are observed, enrollment will be continued without interruption to complete the phase II objective.

Being tested
Regorafenib 40 MG Oral Tablet, Triplet therapy
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Regorafenib 40 MG Oral TabletDrug

    Patients take 2 regorafenib oral tablets of 40 mg daily

  • Triplet therapyDrug

    Regorafenib in combination with BRAF- / MEK- inhibitors

Study groups in NCT05370807
Study groupRoleWhat they receive
Cohort AExperimentalPatients take 2 oral tablets of 40mg of Regorafenib daily.
Receives: Drug: Regorafenib 40 MG Oral Tablet
Cohort BExperimentalPatients take 1 oral tablets of 40mg of Regorafenib daily in combination with BRAF- /MEK- inhibitors dabrafenib/trametinib or encorafenib/binimetinib at the dose they were already taking them.
Receives: Drug: Triplet therapy
Cohort CExperimentalPatients take 1 oral tablets of 40mg of Regorafenib daily in combination with encorafenib/binimetinib at the standard dose.
Receives: Drug: Triplet therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To measure the anti-tumor acitivity of regorafenib treatment in patients with advanced pretreated melanoma.

    Objective response rate (ORR; defined as the percentage of subjects with a confirmed complete response [CR] or partial response [PR] at any time per Response Evaluation Criteria in Solid Tumors [RECIST], version 1.1

    Measured: Through study completion, an average of 1 year.

Secondary outcomes (5)

  1. To measure the progression-free survival (PFS) of study patients treated with regorafenib

    Progression-free survival (PFS; defined as the time from the date of the first dose administration of regorafenib until the earliest date of documented disease progression [per RECIST v1.1] or death due to any cause)

    Measured: Through study completion, an average of 1 year.

  2. To measure the overall survival (OS) of study patients treated with regorafenib

    overall survival (OS; defined as the time from the date of the first dose administration of regorafenib until the date of death due to any cause)

    Measured: Through study completion, an average of 1 year.

  3. Number of AE in study patients

    To count the number of Adverse Events study patients have during the study.

    Measured: Through study completion, an average of 1 year.

  4. To measure the severity of AE in study patients

    Document the grade of all AE in study patients, expressed in grade 1 Mild, 2 Moderate, 3 Severe, 4 Life-Threatening, 5 Death related to AE

    Measured: Through study completion, an average of 1 year.

  5. To measure the Health-Related Quality of Life

    There will be 1 questionnaire used to assess the quality of life. The generic health status of the patients will be assessed by means of the EuroQOL-5D-3L (EQ-5D-3L).

    Measured: Through study completion, an average of 1 year.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 May 2022
  2. Study start3 Oct 2022
  3. Primary completionDec 2026 (estimated)
  4. Study completionMar 2027 (estimated)

Resources

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
Parallel groups
Model description
3 cohorts
Masking
None (open label)
Enrolment
48 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05370807
Sponsor's protocol ID
2022-BN-002
Acronym
RegoMel
Status last verified
May 2026
First submitted
25 Apr 2022
Last updated
30 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Regorafenib 40 MG Oral Tablet and Triplet therapy in people with Melanoma Stage III and Melanoma Stage IV, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.

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 19 inclusion and 20 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: under way, not looking for participants, as of the sponsor's last update on 30 Sep 2026. 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 Belgium. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To measure the anti-tumor acitivity of regorafenib treatment in patients with advanced pretreated melanoma. (time frame: Through study completion, an average of 1 year.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05370807.

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 30 Sep 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in