The trial is looking for new and better ways to treat melanoma, an aggressive type of skin cancer. Having surgery to remove the melanoma will cure the majority of patients with early stage disease. However, a small percentage of these patients will go on to develop further disease, which may spread to other places in their body. Currently, patients who have been cured of melanoma will have appointments in clinic to check that further disease has not developed or returned and some may also receive regular scans. The trial team has developed a blood test that tells us whether cancer cells are still present or is becoming active after a patient has been 'cured' of melanoma, even if a scan looks normal. The test looks for pieces of DNA in the blood that are known to have come from the cancer, which we call 'circulating tumour DNA', or ctDNA. Patients who have ctDNA in their blood have an extremely high chance of the cancer returning. By using the blood test that we have developed we think that we can identify patients earlier than normal. We think that some of the treatments that are used when melanoma cancer has spread may benefit patients at this earlier stage. We want to see if these patients with ctDNA in their blood, who have a higher risk of their cancer returning or spreading, and receive treatment early have a better response to their cancer compared to those patients who receive treatment when their cancer has returned and it can be seen on a scan. This could mean we would be able to offer patients earlier treatment in the future using just a blood test rather than a scan, while also providing reassurance to those patients that do not have ctDNA in their blood that they do not need treatment and their cancer is not returning.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Eligible patients randomised to Arm B will receive 480 mg nivolumab monotherapy 4 weekly via IV infusion for up to 2 years.
The Christie NHS Foundation Trust
Manchester, Greater Manchester, United Kingdom
Overall Survival (OS)
Time frame: From randomisation until death by any cause, assessed up to 84 months.
Relapse Free Survival
Time frame: From randomisation to radiological (recist v1.1)/clinical (confirmed histologically) progression, assessed up to 84 months.
Distant metastasis free survival(DMFS)
Time frame: From randomisation to distant metastatic relapse or death, assessed up to 84 months.
Progression-free survival (PFS) on first line therapy (commenced in Arm A at relapse, and Arm B from randomisation).
Time frame: From start of treatment (day of first dose) until disease progression defined as clinical (confirmed pathologically) or radiological (recist v1.1) progression or death, assessed up to 84 months.
Time from randomisation to disease progression on first line systemic therapy (Arm A first systemic therapy given at relapse, and Arm B nivolumab from randomisation).
Time frame: Time from randomisation to disease progression on first line systemic therapy (Arm A first systemic therapy given at relapse, and Arm B nivolumab from randomisation), assessed up to 84 months.
Radiological response in Arm A (CR, PR, SD and PD) and PD vs. no PD in Arm B to first line systemic therapy.
Time frame: Radiological response in Arm A (CR, PR, SD and PD) and PD vs. no PD in Arm B to first line systemic therapy, assessed up to 84 months.
Time from registration to ctDNA detection.
Time frame: Time from registration to ctDNA detection, assessed at registration and then every 3 months (year 1 to 3) and every 6 months (year 4 and 5).
Number of patients with undetectable ctDNA (not detectable according to the DETECTION assay), but clinical/radiological progression and site of progression (local or distant in addition to organ site).
Time frame: From registration to clinical/radiological progression with undetectable ctDNA, assessed up to 84 months.
RFS of patients with undetectable ctDNA (not randomised) vs. patients with detectable ctDNA in Arm A.
Time frame: From registration to radiological (recist v1.1)/clinical (confirmed histologically) progression in not randomised and in Arm A participants, assessed up to 84 months.
DMFS of patients with undetectable ctDNA (not randomised) vs. patients with detectable ctDNA in Arm A.
Time frame: From registration to distant metastatic relapse or death in not randomised and in Arm A participants, assessed up to 84 months.
OS defined as time from registration until death of patients with undetectable ctDNA (not randomised) vs. patients in Arm A.
Time frame: From registration until death of patients with undetectable ctDNA (not randomised) vs. patients in Arm A, assessed up to 84 months.
To assess treatment-free survival.
Defined as the area between Kaplan-Meier curves between time to first line therapy cessation defined as time from initiation of first line therapy until its cessation and time to subsequent therapy initiation or death defined as time from initiation of first line therapy until initiation of subsequent systemic anticancer therapy or death in Arm A vs. Arm B.
Time frame: Time to first line therapy cessation, assessed up to 84 months.
Toxicity measured according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: From consent until the end of the trial or until disease progression and at least 100 days post the last treatment dose of nivolumab, assessed up to 84 months.
Health economics assessment as assessed by EQ-5D-5L and resource use questionnaires.
Time frame: At registration and every 6 months for both monitoring and post randomisation, with an additional questionnaire at baseline prior to therapy on Arm B and at relapse and every 6 Mo until relapse on first line therapy on Arm A, assessed up to 84 months.
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