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A phase-2 clinical trial of regorafenib in patients with pretreated advanced melanoma
EU CTIS ID: 2024-514087-11-02
What this study is testing
To estimate the anti-tumor activity of regorafenib treatment when added to a BRAF-/MEK-inhibitor combination in patients with advanced pretreated BRAF V600-mutant melanoma at the time of progression on a BRAF-/MEK-inhibitor therapy or for patients who have interrupted this therapy for at least 12 weeks.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- ≥ 18 years of age
- Patients should 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 during screening and within 72 hours prior to first administration of study drug 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. Absolute neutrophil count ≥ 1.2 x 103 /mm3 Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 75 x 103 /mm3 PT/INR and APTTa ≤ 1.5 x ULN Hepatic Albumin ≥ 2.5 g/dL Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN Renal Calculated creatinine clearanceb ≥ 50 mL/min Cardiac Left ventricular ejection fraction ≥ LLN by transthoracic echocardiogram
You likely can't join if
- Patients with uveal melanoma.
- 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.
- 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.
- Ongoing infection CTCAE v5.0 Grade > 2 requiring systemic therapy.
- No enzyme inducing anticonvulsants for ≥ 4 weeks prior to recruitment
- A history or evidence of cardiovascular risk including any of the following: a. Current LVEF < LLN b. QT interval corrected for heart rate using the Bazett’s formula (QTcB) ≥ 480 msec; c. History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with atrial fibrillation controlled for > 30 days prior to recruitment are eligible. d. History (within 6 months prior to recruitment) of acute coronary syndromes (including myocardial infarction or unstable angina), or coronary angioplasty; e. History of deep venous or arterial thrombosis, or CVA the last 6 months f. History or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; g. 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; h. Patients with intra-cardiac defibrillators or permanent pacemakers; i. 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).
See the full eligibility criteria
Who can join
- ≥ 18 years of age
- Patients should 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 during screening and within 72 hours prior to first administration of study drug 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. Absolute neutrophil count ≥ 1.2 x 103 /mm3 Hemoglobin ≥ 9.0 g/dL Platelet count ≥ 75 x 103 /mm3 PT/INR and APTTa ≤ 1.5 x ULN Hepatic Albumin ≥ 2.5 g/dL Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 2.5 x ULN Renal Calculated creatinine clearanceb ≥ 50 mL/min Cardiac Left ventricular ejection fraction ≥ LLN by transthoracic echocardiogram
- Persistent proteinuria of CTCAE v5.0 Grade 3. Urine dipstick result of 3+ or abnormal, based on type of urine test strip used, is allowed if protein excretion (estimated by urine protein/creatinine ratio on a random urine sample) is <3.5 g / 24 hours.
- Signed written informed consent
- Histologically confirmed advanced melanoma that is either stage III (locoregionally metastatic, unresectable) or stage IV (distant 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 a PD-1 blocking immune checkpoint inhibitors (pembrolizumab, nivolumab or other experimental anti-PD-1 antibodies). Patients with BRAF V600mutant 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. Progression of disease per RECIST, version 1.1 [4] or per immune related response criteria [6] must have been documented during this prior treatment.
- 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.
- The presence of at least one measurable lesion per RECIST, version 1.1 [4].
- Interval between the date of the last administration of prior therapy for melanoma and the date of initiation of study treatment: a. ≥ 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; b. ≥ 4 weeks following the date of the last administration of chemotherapy (≥ 6 weeks in case of a nitrosurea or mitomycin C containing regimen); c. 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.
What rules you out
- Patients with uveal melanoma.
- 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.
- 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.
- Ongoing infection CTCAE v5.0 Grade > 2 requiring systemic therapy.
- No enzyme inducing anticonvulsants for ≥ 4 weeks prior to recruitment
- A history or evidence of cardiovascular risk including any of the following: a. Current LVEF < LLN b. QT interval corrected for heart rate using the Bazett’s formula (QTcB) ≥ 480 msec; c. History or evidence of current clinically significant uncontrolled arrhythmias; exception: subjects with atrial fibrillation controlled for > 30 days prior to recruitment are eligible. d. History (within 6 months prior to recruitment) of acute coronary syndromes (including myocardial infarction or unstable angina), or coronary angioplasty; e. History of deep venous or arterial thrombosis, or CVA the last 6 months f. History or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines; g. 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; h. Patients with intra-cardiac defibrillators or permanent pacemakers; i. 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).
- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients
- Female patients who are nursing.
- Cohort-B: patients treated with vemurafenib/cobimetinib.
- Patients who are unable to initiate regorafenib within 4 weeks after interrupting BRAF-/MEK-inhibitor therapy (cohort B) or have not interrupted such therapy for at least 12 weeks (cohort C).Patients with active brain metastases who experience ongoing progressive neurological deterioration or requiring increasing doses of steroids for at least 14 days prior to first dose of study treatment.
- Patients who experienced or are experiencing grade > 3 treatment related adverse events related to BRAF-/MEK-inhibitor therapy.
- Intolerance or drug allergies to tafinlar, mekinist, encorafenib, or binimetinib.
- Any contra-indication for evaluation by whole body 18F-FDG-PET/CT and MRI of the brain.
- 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 nonmelanoma skin cancer.
- Current use of any prohibited medication.
- Administration of an investigational drug within 28 days or 5 half-lives (minimum 14 days), whichever is shorter, prior to recruitment.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.