Metastatic melanoma Cancer Melanoma and other malignant neoplasms of skin
Conditions
Interventions
Population: Patients with advanced (unresectable stage III or IV) melanoma who are due to start (or are within 12 months of starting) anti-PD1 monotherapy as their 1st line treatment
Sponsors
Sheffield Teaching Hospitals NHS Foundation Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Eligibility for REGISTRATION 1. Histologically or cytologically confirmed unresectable AJCC stage III or stage IV (metastatic) melanoma, including cutaneous and non-cutaneous melanoma 2. Aged = 18 years 3. Planned or currently receiving (<12 months) treatment with first-line pembrolizumab or nivolumab 4. Written informed consent for registration Inclusion criteria for RANDOMISATION 1. Registered in DANTE 2. Progression-free by RECIST v1.1 criteria at 12 months (+/- 4 weeks) from the start of pembrolizumab or nivolumab 3. 12 months (+/- 4 weeks) from start of pembrolizumab or nivolumab 4. ECOG performance status 0-2 5. Considered fit by the treating clinician to continue to receive ongoing treatment with pembrolizumab or nivolumab 6. Written informed consent for randomisation
Exclusion criteria
Exclusion criteria: Exclusion criteria for RANDOMISATION 1. Severe comorbidities, including severe autoimmune disease or pneumonitis 2. Active infection requiring systemic therapy 3. Known history of HIV, hepatitis B or C 4. Other malignancy within past 5 years, excluding adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers 5. Pregnant, breast-feeding or patients with reproductive potential (female and male) unwilling to use adequate contraception while receiving anti-PD1 therapy and for 6 months after the last dose. Women of reproductive potential are defined as: following menarche and until becoming post-menopausal, unless permanently sterile. Men of reproductive potential are defined as: post-pubescent and not sterile by vasectomy or bilateral orchidectomy. 6. Prior systemic treatment for advanced melanoma, including ipilimumab and combination ipilimumab and nivolumab, other than BRAF and MEK inhibitors and the current treatment for advanced melanoma. Prior adjuvant or neo-adjuvant therapy is allowed as long as it was completed at least 12 months prior to starting anti-PD1 therapy 7. Treated brain metastases with MRI evidence of progression and/or requirement for high doses of systemic corticosteroids that could result in immunosuppression (> 10 mg/day prednisolone equivalents) 8. Untreated brain metastases that are symptomatic and/or require local intervention (surgery, radiosurgery, corticosteroid therapy) or other systemic therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression-free survival is measured according to RECIST v1.1 at 12 months post-randomisation, using the pre-randomisation (12 month post-start of treatment) scan as the baseline | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Quality of life is measured using the participant self-reported EORTC QLQ-C30, QLQ-MEL38 and the EQ-5D-5L questionnaires at baseline (pre-randomisation), 3, 6, 9, 12, 15 and 18 months post-randomisation (key secondary outcome) 2. Overall survival is calculated from the date of randomisation to the date of death from any cause, or the date last known to be alive for patients who are not known to have died 3. Objective response rate is measured according to RECIST v1.1 at 12 months post-randomisation of the final participant, using the pre-randomisation (12 month post-start of treatment) scan as the baseline 4. Best tumour response rate is measured according to RECIST v1.1 at 12 months post-randomisation of the final participant, using the pre-randomisation (12 month post-start of treatment) scan as the baseline 5. Duration of response is measured according to RECIST v1.1 at 12 months post-randomisation of the final participant, using the pre-randomisation (12 month post-start of treatment) scan as the baseline 6. Safety and toxicity is measured according to CTCAE v5.0 at 12 months and 4 years post-randomisation of the final participant 7. Cost-effectiveness is measured using the incremental cost effectiveness ratio (ICER) and compared against the NICE threshold of £20,000 per QALY. This will be done both within trial (using data collected to 18 months post-randomisation) and across patient lifetime using a Markov model (at 4 years post-randomisation of the final participant | — |
Countries
England, Northern Ireland, Scotland, United Kingdom, Wales
Outcome results
None listed