Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Trametinib

Dabrafenib

Patients take 2 oral tablets of 40mg of Regorafenib daily.

Patients 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.

Patients take 1 oral tablets of 40mg of Regorafenib daily in combination with encorafenib/binimetinib at the standard dose.

Patients take 2 regorafenib oral tablets of 40 mg daily

Regorafenib 40 MG Oral Tablet

Regorafenib in combination with BRAF- / MEK- inhibitors

Triplet therapy

Evelien Vandeurzen, Msc

Evelien Vandeurzen

Bart Neyns, MD, PhD

Iris Dirven, MD

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.

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.

A Clinical Trial of Regorafenib in Patients With Pretreated Advanced Melanoma

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

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

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)

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)

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

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

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).

Spots Global Cancer Trial Database for triplet therapy