Skin Cancer Cancer Malignant neoplasm: skin
Conditions
Interventions
DETECTION will regularly test patients who have had their cancer removed by surgery (every three months for three years and then every six months for a further two years) using blood tests to check fo
Sponsors
Christie Hospital NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study 3. Histological confirmation of cutaneous melanoma 4. Age =18 years 5. Stage IIB or IIC melanoma (sentinel lymph node (SNLB) staged) according to AJCC version 8 (4) 6. Complete resection (including SNLB) must have been performed within 12 weeks prior to registration 7. Disease-free status documented both clinically and radiologically within 4 weeks prior to registration 8. Mutation confirmed in at least one of the following BRAF (p.V600E/p.V600K/p.V600R) /NRAS (p.Q61R/p.Q61K, p.Q61L/p.G12D), which can be tracked in ctDNA with exact point mutation known 9. ECOG performance status 0/1 10. Adequate organ function and screening laboratory values must meet the following criteria: WBC = 2.0x109/L, Absolute neutrophil count (ANC) =1.5x10?/l, Platelets =100 x10?/l, Haemoglobin =90 g/l, Creatinine =1.5 x ULN or creatinine clearance >30 ml/min using Cockcroft-Gault, AST =1.5 x ULN, ALT =1.5 x ULN, Bilirubin =1.5 x ULN unless the patient has familial hyperbilirubinaemia 11. LDH =1.5 x ULN as per local institution parameters 12. Patients who are pregnant or breastfeeding will be eligible to join the trial. However, if they are allocated to Arm B, women of childbearing potential (WOCBP) must agree to have a serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) and must be withdrawn if pregnant or breastfeeding. WOCBP and males who are sexually active with WOCBP must also agree to follow instructions for method(s) of contraception for the duration of treatment plus 5 months if randomised to Arm B (or while receiving any systemic treatment and to follow local guidance if given on Arm A).
Exclusion criteria
Exclusion criteria: 1. If previously received prior immunotherapy, chemotherapy, cancer directed vaccine therapy or BRAF/MEK targeted therapy for cancer 2. Patients with active, known or suspected autoimmune disease. Patients with type 1 diabetes mellitus, rheumatoid arthritis not requiring disease modifying drugs, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger will be permitted to enrol. 3. Current other malignancy or history of another malignancy within the last 3 years. Patients who have been disease-free for 3 years, (i.e. patients with second malignancies that have been definitively treated at least 3 years ago) or patients with a history of completely resected non-melanoma skin cancer are eligible 4. Any serious or unstable pre-existing medical conditions (aside from malignancy exceptions specified above), psychiatric disorders, or other conditions that could interfere with the patient’s safety, obtaining informed consent, or compliance with study procedures 5. Patients with a condition requiring ongoing/long-term (> 3 months) systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement steroid doses =10 mg daily prednisolone equivalent are permitted in the absence of active autoimmune disease 6. Patients with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity 7. History of allergies or adverse drug reaction to any of the study drug components or to any monoclonal antibody 8. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection 9. Prisoners or patients who are involuntarily incarcerated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival (OS) defined as the time from randomisation until death from any cause measured as the incidence of death at follow up after relapse (every 12 weeks after the date of confirmed relapse) | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Recurrence free survival (RFS) defined as the time from randomisation to radiological or clinical progression measured using scans evaluated using the RECIST v1.1 criteria at screening, every 6 months for years 1 to 5, and at follow up from the date of confirmed relapse as part of standard of care, with up to 3 per year after this based on clinical need; or histological data (i.e. biopsies) when clinically indicated 2. Distant metastasis-free survival (DMFS) defined as the time from randomisation to distant metastatic relapse or death measured using scans evaluated using the RECIST v1.1 criteria at screening, every 6 months for years 1 to 5, and at follow up from the date of confirmed relapse as part of standard of care, with up to 3 per year after this based on clinical need; or histological data (i.e. biopsies) when clinically indicated 3. Progression Free Survival (PFS) for participants on first-line therapy (from relapse for participants in Arm A, from randomisation for participants in Arm B) defined as the time from start of treatment (day of the first dose) until disease progression as clinical or radiological progression or death measured using scans evaluated using the RECIST v1.1 criteria at screening, every 6 months for years 1 to 5, and at follow up from the date of confirmed relapse as part of standard of care, with up to 3 per year after this based on clinical need; or histological data (i.e. biopsies) when clinically indicated 4. Time from randomisation to disease progression of first-line therapy (from relapse for participants in Arm A, from randomisation for participants in Arm B) measured using scans evaluated using the RECIST v1.1 criteria at screening, every 6 months for years 1 to 5, and at follow up from the date of confirmed relapse as part of standard of care, with up to 3 per year after this based on clinical need; or histological data (i.e. biopsies) when clinically indicated | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Contacts
Public ContactSilviya Balabanova
Outcome results
None listed