Condition category
Cancer
Date applied
15/01/2018
Date assigned
31/07/2018
Last edited
18/07/2019
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Dr Sue Bell

ORCID ID

Contact details

Clinical Trials Research Unit
Leeds Institute of Clinical Trials Research
University of Leeds
Leeds
LS2 9JT
United Kingdom
+44 (0)113 343 1492
s.e.bell@leeds.ac.uk

Additional identifiers

EudraCT number

2017-002435-42

ClinicalTrials.gov number

Protocol/serial number

35180

Study information

Scientific title

DANTE: A randomised phase III trial to evaluate the Duration of ANti-PD1 monoclonal antibody Treatment in patients with metastatic mElanoma

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

East Midlands – Leicester South Research Ethics Committee, 18/01/2018, ref: 17/EM/0440

Study design

Randomised; Interventional; Design type: Treatment, Drug, Immunotherapy, Active Monitoring

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

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

Phase

Phase IV

Drug names

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 trial start date

01/02/2017

Overall trial end date

31/05/2027

Reason abandoned (if study stopped)

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 1208; UK Sample Size: 1208

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

13/08/2023

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Weston Park Hospital (lead centre)
Whitham Rd
Sheffield
S10 2SJ
United Kingdom

Trial participating centre

Addenbrooke's Hospital
Hills Rd
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Rd
Glasgow
G12 0YN
United Kingdom

Trial participating centre

Belfast City Hospital
10 Jubilee Rd
Belfast
BT9 7JL
United Kingdom

Trial participating centre

Broomfield Hospital
Court Rd Broomfield
Chelmsford
CM1 7ET
United Kingdom

Trial participating centre

Castle Hill Hospital
Castle Rd
Cottingham
HU16 5JQ
United Kingdom

Trial participating centre

Charing Cross Hospital
Fulham Palace Rd Hammersmith
London
W6 8RF
United Kingdom

Trial participating centre

Cheltenham General Hospital
Sandford Rd
Cheltenham
GL53 7AN
United Kingdom

Trial participating centre

Churchill Hospital
Old Rd Headington
Oxford
OX3 7LE
United Kingdom

Trial participating centre

City Hospital
Hucknall Rd
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Rd Crownhill
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Freeman Hospital
Freeman Rd High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom

Trial participating centre

Gloucestershire Royal Hospital
Great Western Rd
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

Kent & Canterbury Hospital
Ethelbert Rd
Canterbury
CT1 3NG
United Kingdom

Trial participating centre

Mount Vernon Hospital
Rickmansworth Rd
Northwood
HA6 2RN
United Kingdom

Trial participating centre

Ninewells Hospital
James Arrott Dr
Dundee
DD2 1SY
United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital
Colney Ln
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Queen Alexandra Hospital
Southwick Hill Rd Cosham
Portsmouth
PO6 3LY
United Kingdom

Trial participating centre

Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom

Trial participating centre

Queen Elizabeth Queen Mother Hospital
St Peter's Rd
Margate
CT9 4AN
United Kingdom

Trial participating centre

Raigmore Hospital
Old Perth Rd
Inverness
IV2 3UJ
United Kingdom

Trial participating centre

Royal Cornwall Hospital
Treliske
Truro
TR1 3LQ
United Kingdom

Trial participating centre

Royal Derby Hospital
Uttoxeter Rd
Derby
DE22 3NE
United Kingdom

Trial participating centre

Royal Devon and Exeter Hospital
Barrack Rd
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Royal Free Hospital
Pond St Hampstead
London
NW3 2QG
United Kingdom

Trial participating centre

Royal Preston Hospital
Sharoe Green Lane North Fulwood
Preston
PR2 9HT
United Kingdom

Trial participating centre

Royal Stoke University Hospital
Newcastle Rd
Stoke-on-Trent
ST4 6QG
United Kingdom

Trial participating centre

Royal Sussex County Hospital
Eastern Rd
Brighton
BN2 5BE
United Kingdom

Trial participating centre

Southampton General Hospital
Tremona Rd
Southampton
SO16 6YD
United Kingdom

Trial participating centre

St Helens Hospital
Marshalls Cross Rd
Saint Helens
WA9 3DA
United Kingdom

Trial participating centre

St James's University Hospital
Beckett St
Leeds
LS9 7TF
United Kingdom

Trial participating centre

The Christie
Wilmslow Rd
Manchester
M20 4BX
United Kingdom

Trial participating centre

The Clatterbridge Cancer Centre
Clatterbridge Rd Birkenhead
Wirral
CH63 4JY
United Kingdom

Trial participating centre

Velindre Hospital
Velindre Rd
Cardiff
CF14 2TL
United Kingdom

Trial participating centre

William Harvey Hospital
Kennington Rd Willesborough
Ashford
TN24 0LZ
United Kingdom

Sponsor information

Organisation

Sheffield Teaching Hospitals NHS Foundation Trust

Sponsor details

c/o Dr Dipak Patel
Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom
+44 (0)114 2265941
Dipak.Patel@sth.nhs.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

National government

Location

United Kingdom

Results and Publications

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 statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/02/2025

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

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.