DANTE: Duration of Anti-PD1 therapy for melanoma
| ISRCTN | ISRCTN15837212 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15837212 |
| EudraCT/CTIS number | 2017-002435-42 |
| Secondary identifying numbers | 35180 |
- Submission date
- 15/01/2018
- Registration date
- 31/07/2018
- Last edited
- 14/10/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Contact information
Dr Sue Bell
Scientific
Scientific
Clinical Trials Research Unit
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
| Phone | +44 (0)113 343 1492 |
|---|---|
| s.e.bell@leeds.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug, Immunotherapy, Active Monitoring |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | DANTE: A randomised phase III trial to evaluate the Duration of ANti-PD1 monoclonal antibody Treatment in patients with metastatic mElanoma |
| Study acronym | DANTE |
| Study hypothesis | This trial aims to determine whether anti-PD1 monotherapy to treat advanced melanoma can be stopped after 1 year, rather than the current standard practice (i.e. continuing to treat until disease progression/unacceptable toxicity, or for at least 2 years), and achieve and maintain as good an outcome (in terms of the cancer coming back). The hypothesis is that continuing treatment beyond 1 year is unnecessary, as there is no biological evidence that justifies continuous therapy; many responses occur in the first year and can continue even after treatment is stopped. Also, continuing treatment exposes patients to an increased risk of developing immune-related toxicities and is a considerable burden to patients and the National Health Service. |
| Ethics approval(s) | East Midlands – Leicester South Research Ethics Committee, 18/01/2018, ref: 17/EM/0440 |
| Condition | Metastatic melanoma |
| Intervention | 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 Consenting patients will be registered with the CTRU within the first 12 months of starting anti-PD1 monotherapy. The registration phase is not considered part of this clinical trial. Patients will receive anti-PD1 monotherapy and undergo monitoring and scans as per standard of care. When they are approaching 12 months of treatment, patients who have not progressed and remain on treatment will be approached for formal eligibility assessment and be consented for randomisation into the trial. Baseline (pre-randomisation) assessments: 1. CT scan at 12 months post start of treatment (standard practice) 2. Quality of life and health economics questionnaire completion Intervention: Stop anti-PD1 therapy at randomisation (12 months after starting therapy) Comparator (control): Continue anti-PD1 therapy until disease progression or unacceptable toxicity (or a minimum of 2 years in the absence of progression/unacceptable toxicity) Follow-up assessments 1. Every 3 months for the first 12 months post randomisation, then every 6 months in years 2 to 4 post-randomisation. A CT and/or MRI scan will be performed at each timepoint (standard practice) 2. Patients will complete quality of life and health economic questionnaires every 3 months until 18 months post-randomisation |
| Intervention type | Other |
| Primary outcome measure | 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 outcome measures | 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 |
| Overall study start date | 01/02/2017 |
| Overall study end date | 15/10/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1208; UK Sample Size: 1208 |
| Participant 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 |
| Participant 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 |
| Recruitment start date | 13/08/2018 |
| Recruitment end date | 15/09/2023 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Weston Park Hospital (lead centre)
Whitham Rd
Sheffield
S10 2SJ
United Kingdom
Sheffield
S10 2SJ
United Kingdom
Addenbrooke's Hospital
Hills Rd
Cambridge
CB2 0QQ
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Western Rd
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
Belfast City Hospital
10 Jubilee Rd
Belfast
BT9 7JL
United Kingdom
Belfast
BT9 7JL
United Kingdom
Broomfield Hospital
Court Rd
Broomfield
Chelmsford
CM1 7ET
United Kingdom
Broomfield
Chelmsford
CM1 7ET
United Kingdom
Castle Hill Hospital
Castle Rd
Cottingham
HU16 5JQ
United Kingdom
Cottingham
HU16 5JQ
United Kingdom
Charing Cross Hospital
Fulham Palace Rd
Hammersmith
London
W6 8RF
United Kingdom
Hammersmith
London
W6 8RF
United Kingdom
Cheltenham General Hospital
Sandford Rd
Cheltenham
GL53 7AN
United Kingdom
Cheltenham
GL53 7AN
United Kingdom
Churchill Hospital
Old Rd
Headington
Oxford
OX3 7LE
United Kingdom
Headington
Oxford
OX3 7LE
United Kingdom
City Hospital
Hucknall Rd
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Derriford Hospital
Derriford Rd
Crownhill
Plymouth
PL6 8DH
United Kingdom
Crownhill
Plymouth
PL6 8DH
United Kingdom
Freeman Hospital
Freeman Rd
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Gloucestershire Royal Hospital
Great Western Rd
Gloucester
GL1 3NN
United Kingdom
Gloucester
GL1 3NN
United Kingdom
Kent & Canterbury Hospital
Ethelbert Rd
Canterbury
CT1 3NG
United Kingdom
Canterbury
CT1 3NG
United Kingdom
Mount Vernon Hospital
Rickmansworth Rd
Northwood
HA6 2RN
United Kingdom
Northwood
HA6 2RN
United Kingdom
Ninewells Hospital
James Arrott Dr
Dundee
DD2 1SY
United Kingdom
Dundee
DD2 1SY
United Kingdom
Norfolk and Norwich University Hospital
Colney Ln
Norwich
NR4 7UY
United Kingdom
Norwich
NR4 7UY
United Kingdom
Queen Alexandra Hospital
Southwick Hill Rd
Cosham
Portsmouth
PO6 3LY
United Kingdom
Cosham
Portsmouth
PO6 3LY
United Kingdom
Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Birmingham
B15 2TH
United Kingdom
Queen Elizabeth Queen Mother Hospital
St Peter's Rd
Margate
CT9 4AN
United Kingdom
Margate
CT9 4AN
United Kingdom
Raigmore Hospital
Old Perth Rd
Inverness
IV2 3UJ
United Kingdom
Inverness
IV2 3UJ
United Kingdom
Royal Cornwall Hospital
Treliske
Truro
TR1 3LQ
United Kingdom
Truro
TR1 3LQ
United Kingdom
Royal Derby Hospital
Uttoxeter Rd
Derby
DE22 3NE
United Kingdom
Derby
DE22 3NE
United Kingdom
Royal Devon and Exeter Hospital
Barrack Rd
Exeter
EX2 5DW
United Kingdom
Exeter
EX2 5DW
United Kingdom
Royal Free Hospital
Pond St
Hampstead
London
NW3 2QG
United Kingdom
Hampstead
London
NW3 2QG
United Kingdom
Royal Preston Hospital
Sharoe Green Lane North
Fulwood
Preston
PR2 9HT
United Kingdom
Fulwood
Preston
PR2 9HT
United Kingdom
Royal Stoke University Hospital
Newcastle Rd
Stoke-on-Trent
ST4 6QG
United Kingdom
Stoke-on-Trent
ST4 6QG
United Kingdom
Royal Sussex County Hospital
Eastern Rd
Brighton
BN2 5BE
United Kingdom
Brighton
BN2 5BE
United Kingdom
Southampton General Hospital
Tremona Rd
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
St Helens Hospital
Marshalls Cross Rd
Saint Helens
WA9 3DA
United Kingdom
Saint Helens
WA9 3DA
United Kingdom
St James's University Hospital
Beckett St
Leeds
LS9 7TF
United Kingdom
Leeds
LS9 7TF
United Kingdom
The Christie
Wilmslow Rd
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
The Clatterbridge Cancer Centre
Clatterbridge Rd
Birkenhead
Wirral
CH63 4JY
United Kingdom
Birkenhead
Wirral
CH63 4JY
United Kingdom
Velindre Hospital
Velindre Rd
Cardiff
CF14 2TL
United Kingdom
Cardiff
CF14 2TL
United Kingdom
William Harvey Hospital
Kennington Rd
Willesborough
Ashford
TN24 0LZ
United Kingdom
Willesborough
Ashford
TN24 0LZ
United Kingdom
Sponsor information
Sheffield Teaching Hospitals NHS Foundation Trust
Hospital/treatment centre
Hospital/treatment centre
c/o Dr Dipak Patel
Northern General Hospital
Herries Road
Sheffield
S5 7AU
England
United Kingdom
| Phone | +44 (0)114 2265941 |
|---|---|
| Dipak.Patel@sth.nhs.uk | |
"ROR" |
https://ror.org/018hjpz25 |
Funders
Funder type
Government
National Institute for Health Research
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | The study protocol will be published. Planned publication of the study results in a high-impact peer reviewed journal. Primary analysis publication anticipated February 2025. Long-term results publication anticipated February 2028. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 01/07/2021 | 05/07/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
14/10/2022: The following changes were made to the trial record:
1. The recruitment end date was changed from 13/08/2023 to 15/09/2023.
2. The overall end date was changed from 31/05/2027 to 15/10/2024.
3. Note from contact: Trial closed early by the funder before the target sample size reached, due to slow recruitment and inability to recruit to target within an acceptable time frame.
Registrations closed 30/09/2022. Randomisation system remains open for participants registered by 30/09/2022. Anticipated final number of participants randomised: 151-209 participants. Latest possible date of randomisation: 15/09/2023.
05/07/2021: Publication reference added.
18/07/2019: The plain English summary was added.
21/06/2019: Internal review.
05/04/2019: Internal review.
22/03/2019: The condition was updated from "Specialty: Cancer, Primary sub-specialty: Skin Cancer; UKCRC code/ Disease: Cancer/ Melanoma and other malignant neoplasms of skin" to "Metastatic melanoma".
05/03/2019: Internal review.
