The purpose of this study is to investigate the side effects and safety, and effectiveness of combining dabrafenib and trametinib with radiotherapy.
Previous and ongoing clinical trials have demonstrated the effectiveness and safety of combining both dabrafenib and trametinib compared with dabrafenib alone. This has led to the approval for the use of both drugs in combination in people with metastatic melanoma with the BRAF mutation. Melanoma that has spread to other parts of the body may also benefit from radiotherapy to help reduce symptoms from melanoma. Previous studies have shown that melanoma may be sensitive to radiotherapy and that it can help to improve quality of life.
The intention of the CombiRT study is to establish if dabrafenib, trametinib and radiotherapy combined is a safe and effective treatment for metastatic melanoma.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. ≥18 years of age.
. Signed written informed consent.
. Histologically confirmed cutaneous melanoma that is either Stage IIIC (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E/K mutation-positive as determined by a BRAF mutation assay.
. Have received dabrafenib and trametinib for 2 weeks or more prior to enrolment in the study (i.e. first fraction of palliative RT), and is still continuing with dabrafenib and trametinib.
. Symptomatic or bulky (greater than 2 cm in diameter) soft tissue, nodal or bony metastases requiring palliative RT.
. Have measurable disease according to RECIST 1.1 criteria. Note: patients with bony metastases that are not measurable by RECIST 1.1 criteria are allowed in this study.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Toxicity profile for patients receiving dabrafenib and trametinib in combination with RT, by measuring adverse events and radiotherapy associated toxicities.
. All anti-cancer treatment-related toxicities (except alopecia and laboratory values as listed on Table 1 in protocol) must be less than or equal to (≤) Grade 1 according to the Common Terminology Criteria for Adverse Events version 4 (CTCAE version 4.03; NCI, 2009) at the time of study enrolment.
. 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.
Exclusion criteria
. Treatment with Ipilimumab or any other anti-CTLA-4 monoclonal antibody therapy within the past 4 weeks.
. Treatment with anti-PD-1 or anti-PD-L1 monoclonal antibody therapy within the past 4 weeks.
. Known ocular or primary mucosal melanoma.
. Four (4) or more lesions requiring palliative RT at the time of study enrolment.
. Symptomatic brain metastases or those treated \< 3 months previously.
. Clear evidence of systemic disease progression on dabrafenib and trametinib.
. Systemic anti-cancer treatment (chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment) within the last 4 weeks. Prior interferon treatment in the adjuvant setting is allowed.
. Current use of a prohibited medication (list of prohibited medications in protocol).