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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Mr
Samuel
Resendez
+44 (0)1223 216083
cuh.cctu.premium@nhs.net
Dr
Pippa
Corrie
+44 (0)1223 274013
philippa.corrie@nhs.net
More information about this study, what is involved and how to take part can be found on the study website.
Melanoma
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Background and study aims
Patients who are planned to undergo surgery to remove melanoma that has spread to lymph nodes or other parts of their body are routinely offered a course of anticancer drug treatment after their surgery, which lasts for up to 52 weeks. This is called adjuvant therapy. The aim of this study is to determine if starting treatment before surgery is beneficial. This is called neoadjuvant therapy. Patients will be given either an 8-week course of treatment before surgery, and then up to 44 weeks further treatment after surgery (a total of 52 weeks). The study will also look at how willing patients and doctors are to take part in a trial looking at starting treatment prior to surgery compared with standard treatment given after surgery.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
Current inclusion criteria as of 16/05/2025:
1. Written informed consent to participate
2. Aged ≥18 years old
3. AJCC 8th edition stage III (B/C/D), or extracranial oligometastatic stage IV BRAFV600 mutant melanoma, based on histological/cytological and radiological assessments for which surgery is planned, and resection is expected to remove all known tumour(s) with R0 resection margins. ‘Oligometastatic stage IV’ is defined for the purpose of this trial as M stage disease confined to a single body organ excluding the brain that can be readily removed surgically with anticipated clear margins
4. For stage III patients, confirmation of no evidence of distant metastatic disease using preferred imaging modalities including CT body or PET/CT and CT or MRI head
5. For stage IV patients, confirmation of no evidence of unresectable metastatic disease, or metastatic disease in more than 1 body organ, using preferred imaging modalities including CT body or PET/CT and CT or MRI head. The site of metastasis should not be in bone, or CNS, or in any other body site where complete resection is not feasible
6. The planned resectable disease must be radiologically measurable using standard imaging modalities
7. Baseline tumour assessments must be done within 28 days prior to registration
8. BRAF V600 mutation confirmed by PCR or NGS
9. Received no prior BRAF or MEK inhibitors
10. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (see Appendix 3 – Karnofsky and ECOG Performance Status Scale)
11. Predicted life expectancy >12 months
12. Normal QTc interval (<480 msec) on ECG and left ventricular ejection fraction within normal limits, assessed by echocardiogram or MUGA
13. Adequate bone marrow function defined as:
13.1. Absolute neutrophil count (ANC) ≥1.5 x 10e9/l
13.2. Haemoglobin (Hb) ≥90 g/l
13.3. Platelets ≥100 x 10e9 /l
14. Adequate liver function defined as:
14.1. Aspartate aminotransferase (AST) and/or alanine transaminase (ALT) ≤2.5 x upper limit of normal range (ULN)
14.2. Total bilirubin <1.5 x ULN (except if the patient has Gilbert Syndrome or liver metastases, in which case the bilirubin must be <3 x ULN)
15. Adequate renal function defined as:
15.1. Serum creatinine ≤1.5 x ULN or
15.2. Calculated creatinine clearance by Cockcroft-Gault of ≥40 ml/min
16. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, completion of QoL and PROM questionnaires and other procedures described in the protocol
17. Women of child-bearing potential (WCBP) and all sexually active male patients must agree to use effective contraception methods throughout treatment as per section 11.10 of this protocol
18. Ability to swallow the trial medication
19. Confirmation of adequate diagnostic tumour tissue available for researc
You may not be able to take part if:
Current exclusion criteria as of 16/05/2025:
1. Prior adjuvant therapy for resected primary or locoregional melanoma2. Other invasive malignancies diagnosed within the last 2 years which are not in complete remission, or for which additional therapy is required3. Brain or bone metastases4. Non-cutaneous primary site of melanoma5. Prior radiotherapy to the site planned for surgery6. History or current evidence of retinal vein occlusion (RVO) or risk factors for RVO (uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)7. Left ventricular function < 50%8. Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:8.1. Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months8.2. Uncontrolled hypertension8.3. Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHA) III or IV, see Appendix 4) or frequent angina8.4. Patients with baseline QTC interval > 480 msec on electrocardiogram (ECG)8.5. Left ventricular ejection fraction below the lower limit of normal8.6. Presence of active infection8.7. Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C9. Known allergy or hypersensitivity to Encorafenib or Binimetinib, or their excipients. Binimetinib contains lactose, so patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption will be excluded10. Women who are pregnant, plan to become pregnant or are lactating during the trial period11. Use of other investigational anti-cancer drugs (a washout period of 28 days would be required)12. Use of strong inducers and inhibitors of CYP3A4 (Appendix 5 – Prohibited Medication)13. Known HIV or active Hep B or Hep C infection14. Patients who have neuromuscular disorders associated with elevated creatine phosphokinase (CK, e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)15. Autoimmune conditions requiring regular or intermittent use of any systemic steroid or immunosuppressive drugs, with the exception of steroid inhalers16. Any immunotherapy in the last 3 months17. Prior radiotherapy to the site of disease planned for resection18. Concurrent participation in an interventional clinical trial (observational studies are allowed)
_____
Previous exclusion criteria:
1. Prior adjuvant therapy for resected primary or locoregional melanoma2. Other invasive malignancies diagnosed within the last 2 years which are not in complete remission, or for which additional therapy is required 3. Brain or bone metastases4. Non-cutaneous primary site of melanoma5. Prior radiotherapy to the site planned for surgery6. History or current evidence of retinal vein occlusion (RVO) or risk factors for RVO (uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)7. Left ventricular function < 50%8. Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:8.1. Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months8.2. Uncontrolled hypertension8.3. Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV, see Appendix 3) or frequent angina 8.4. Patients with baseline QTC interval > 480 msec on electrocardiogram (ECG)8.5. Left ventricular ejection fraction below the lower limit of normal 8.6. Presence of active infection 8.7. Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C9. Known allergy or hypersensitivity to Encorafenib or Binimetinib, or their excipients. Binimetinib contains lactose, so patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption will be excluded10. Women who are pregnant, plan to become pregnant or are lactating during the trial period11. Use of other investigational anti-cancer drugs (a washout period of 28 days would be required)12. Use of strong inducers and inhibitors of CYP3A4 (Appendix 4 – Prohibited Medication) 13. Known HIV or active Hep B or Hep C infection14. Patients who have neuromuscular disorders associated with elevated creatine phosphokinase (CK, e.g. inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)15. Autoimmune conditions requiring regular or intermittent use of any systemic steroid or immunosuppressive drugs, with the exception of steroid inhalers16. Any immunotherapy in the last 3 months17. Prior radiotherapy to the site of disease planned for resection18. Concurrent participation in an interventional clinical trial (observational studies allowed)
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Mr
Samuel
Resendez
+44 (0)1223 216083
cuh.cctu.premium@nhs.net
Dr
Pippa
Corrie
+44 (0)1223 274013
philippa.corrie@nhs.net
More information about this study, what is involved and how to take part can be found on the study website.
The study is sponsored by Cambridge University Hospitals NHS Foundation Trust and funded by Les Laboratories Pierre Fabre.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
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