Phase 2 Melanoma Trial, Recruiting

Written by an AI model from ClinicalTrials.gov eligibility criteria and checked on a sample basis. Please confirm against the original criteria.

Who might be able to join this trial:

• People aged 18 or older at the time of giving consent to participate.
• People who are able to provide written consent to participate (if someone cannot write their consent due to an impairment, the trial site may be able to follow local procedures to obtain consent in another way).
• People who have been diagnosed with skin melanoma (confirmed by tissue testing) that has spread to the brain (confirmed by imaging).
• People whose tumour has been tested and found to have a specific gene change — in RAS, BRAF, or NF1 — or has none of these changes (called "triple wildtype"), using an approved testing method.
• People who have at least one brain tumour that has not previously been treated with surgery or radiation, measuring between 0.5 cm and 4 cm across on a specific type of brain scan (gadolinium-enhanced MRI). Prior treatment of other brain tumours is allowed.
• People who have already received at least one course of immunotherapy as a systemic (whole-body) treatment.
• People in Cohort B (BRAF mutation group) who have already received one or more treatments with BRAF or MEK inhibitor medicines.
• People who are in reasonably good general health, as measured by standard medical performance scales (ECOG score of 0 or 1, or Karnofsky score of 70 or above).
• People whose blood counts, liver, kidney, and heart function meet the required levels on laboratory tests, including adequate white blood cells, haemoglobin, platelets, liver enzymes, bilirubin, kidney function markers, and heart pumping function of at least 55%.
• People whose blood clotting levels are within acceptable ranges (if not on blood-thinning treatment).
• Women who could become pregnant must have a negative pregnancy blood test before joining and agree to use a highly effective form of contraception during the study and for 90 days after the last dose of the study drug.
• Men who could father a child must take steps to avoid pregnancy in partners who could become pregnant during the study and for at least 90 days after stopping treatment (or longer if required by local authorities).
• People who have recovered from side effects of previous treatments to a mild or minimal level before starting the trial, with exceptions allowed for hair loss and mild-to-moderate nerve-related symptoms.

Who may not be able to join:

• People who are currently taking part in another clinical trial using an investigational treatment.
• People who have had systemic cancer treatment or any investigational therapy within the past 28 days (or within five half-lives of the drug, whichever is shorter) before starting the study.
• People who are experiencing significant neurological symptoms clearly linked to an untreated brain tumour.
• People with a known allergy or serious reaction to any of the study drugs or their ingredients.
• People who are unable to swallow and keep down the study medication.
• People whose melanoma is of the uveal (eye) or mucosal (internal lining) type.
• People who have had, or currently have, cancer spread to the lining around the brain and spinal cord (leptomeningeal metastases).
• People with certain heart rhythm measurements (QTcF interval) above specified thresholds on an ECG — above 450 ms for males and above 470 ms for females.
• People who have had a significant bleeding event (Grade 3 or higher, or Grade 2 bleeding in the brain) within the four weeks before starting the study.
• People with serious or uncontrolled heart conditions, including recent heart attack, heart surgery, unstable chest pain, serious heart rhythm problems, heart failure, or high blood pressure that cannot be controlled with medication.
• People with a history of certain lung conditions, including interstitial lung disease, pulmonary fibrosis, sarcoidosis, silicosis, lung hypersensitivity, or significant fluid around the lungs.
• People with an active or uncontrolled autoimmune disease that required treatment in the past two years (such as lupus, scleroderma, or autoimmune hepatitis).
• People with HIV who have had a detectable level of the virus within the past six months. People with HIV whose virus is well controlled on treatment may be eligible (confirm with trial site).
• People with active tuberculosis, active hepatitis B infection, or active hepatitis C infection. People with certain past or resolved infections may still be eligible (confirm with trial site).
• People with a history of a bleeding disorder (unrelated to blood-thinning medication).
• People with an ongoing or active uncontrolled infection or illness.
• People who, in the treating doctor's judgement, would be unlikely to follow the study requirements.
• People with an active skin condition that has needed systemic treatment in the past year.
• People with a history of a serious muscle-breakdown condition called rhabdomyolysis.
• People with certain eye conditions, including glaucoma, history of or risk factors for retinal vein blockage, uncontrolled diabetes, significant retinal disease, elevated eye pressure above 21 mmHg, or serious corneal conditions that could make it difficult to monitor for eye-related side effects.
• People with a known allergy or sensitivity to any of the specific study drugs: avutometinib, defactinib, or encorafenib, or their inactive ingredients.
• People who have taken certain medications, supplements, herbal remedies, or foods that could interact with the study drugs within 14 days before starting treatment, including strong inhibitors or inducers of specific liver enzymes (CYP3A4, CYP2C9) or drug transport proteins (P-gp, BCRP).
• People who are currently taking warfarin (a blood-thinning medication) and cannot stop taking it.
• People taking other prohibited medications, including other anticancer therapies or colony-stimulating factors, without an adequate washout period before starting the study.
• People who have been diagnosed with another cancer within the past two years, unless it has been fully treated with no signs of disease and requires no further treatment during the study. Some lower-risk cancers may be exceptions (confirm with trial site).
• People with any other condition that the treating doctor believes would make participation unsafe or make it difficult to follow study procedures (such as active infection, bowel obstruction, inability to swallow tablets, or social and psychological barriers).
• People with medical, psychiatric, or cognitive conditions that may affect their ability to understand the study, give informed consent, or follow the study protocol.

Important: Always verify eligibility with the trial site directly before applying.