RegoMel: A Clinical Trial of Regorafenib in Patients With Pretreated Advanced Melanoma
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Regorafenib Patients take 2 oral tablets of 40mg of Regorafenib daily. |
Drug: Regorafenib 40 MG Oral Tablet
Patients take 2 regorafenib oral tablets of 40 mg daily
|
Outcome Measures
Primary Outcome Measures
- To measure the anti-tumor acitivity of regorafenib treatment in patients with advanced pretreated melanoma. [Through study completion, an average of 1 year.]
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
Secondary Outcome Measures
- To measure the progression-free survival (PFS) of study patients treated with regorafenib [Through study completion, an average of 1 year.]
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)
- To measure the overall survival (OS) of study patients treated with regorafenib [Through study completion, an average of 1 year.]
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)
- Number of AE in study patients [Through study completion, an average of 1 year.]
To count the number of Adverse Events study patients have during the study.
- To measure the severity of AE in study patients [Through study completion, an average of 1 year.]
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
- To measure the Health-Related Quality of Life [Through study completion, an average of 1 year.]
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).
Eligibility Criteria
Criteria
Inclusion Criteria:
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- ≥ 18 years of age. 2. Signed written informed consent. 3. Histologically confirmed advanced melanoma that is either stage III (unresectable) or stage IV (metastatic, unresectable) 4. 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
- 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.
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The presence of at least one measurable lesion per RECIST, version 1.1 (Eisenhauer et al. Eur J Cancer 2009) 6. Interval between the date of the last administration of prior therapy for melanoma and the date of recruitment:
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≥ 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;
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≥ 4 weeks following the date of the last administration of chemotherapy (≥ 6 weeks in case of a nitrosurea or mitomycin C containing regimen);
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14 days following the date of the last administration of targeted therapy with BRAF/MEK-inhibition.
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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.
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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.
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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.
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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.
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An Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Oken et al, Am J Clin Oncol 1982).
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Adequate baseline organ function as defined in Table 1. 13. Negative proteinuria on dipstick or 24 hours proteinuria <1000mg.
Exclusion Criteria:
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- 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).
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Any contra-indication for evaluation by whole body 18F-FDG-PET/CT or MRI of the brain.
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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.
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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.
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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.
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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.
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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:
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Current LVEF < LLN
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A QT interval corrected for heart rate using the Bazett's formula (QTcB) ≥ 480 msec;
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A history or evidence of current clinically significant uncontrolled arrhythmias. Exception: subjects with atrial fibrillation controlled for > 30 days prior to recruitment are eligible.
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A history (within 6 months prior to recruitment) of acute coronary syndromes (including myocardial infarction or unstable angina), or coronary angioplasty;
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History of deep venous or arterial thrombosis, or CVA the last 6 months
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A history or evidence of current ≥ Class II congestive heart failure as defined by the New York Heart Association (NYHA) guidelines;
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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;
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Patients with intra-cardiac defibrillators or permanent pacemakers;
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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).
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Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO).
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Female patients who are nursing.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UZ Brussels | Jette | Brussel | Belgium | 1090 |
Sponsors and Collaborators
- Universitair Ziekenhuis Brussel
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2022-BN-002