Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-002435-42
    Sponsor's Protocol Code Number:STH19290
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:GB - no longer in EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-05-17
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2017-002435-42
    A.3Full title of the trial
    DANTE: A randomised phase III trial to evaluate the Duration of ANti-PD1 monoclonal antibody Treatment in patients with metastatic mElanoma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    DANTE - A trial to assess the length of anti-PD1 therapy for metastatic melanoma
    A.3.2Name or abbreviated title of the trial where available
    DANTE (Duration of Anti-PD1 therapy for melanoma)
    A.4.1Sponsor's protocol code numberSTH19290
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSheffield Teaching Hospitals NHS Foundation Trust
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNational Institute of Health Research (Health Technology Assessment)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationClinical Trials Research Unit (CTRU), University of Leeds
    B.5.2Functional name of contact pointDr Sue Bell
    B.5.3 Address:
    B.5.3.1Street AddressClinical Trials Research Unit, University of Leeds
    B.5.3.2Town/ cityLeeds
    B.5.3.3Post codeLS2 9JT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number01133431492
    B.5.5Fax number01133430686
    B.5.6E-mails.e.bell@leeds.ac.uk
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderMerck Sharp & Dohme Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePembrolizumab
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPembrolizumab
    D.3.9.1CAS number 1374853-91-4
    D.3.9.4EV Substance CodeAS1
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Pharma EEIG
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameNivolumab
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous drip use (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNNivolumab
    D.3.9.1CAS number 946414-94-4
    D.3.9.4EV Substance CodeAS2
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced (unresectable stage III or stage IV (metastatic)) melanoma
    E.1.1.1Medical condition in easily understood language
    Advanced melanoma (stage III or stage IV)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10025670
    E.1.2Term Malignant melanoma stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10025671
    E.1.2Term Malignant melanoma stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10068117
    E.1.2Term Metastatic ocular melanoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This trial is for patients with advanced melanoma (skin cancer) who are being treated with ‘anti-PD1’ drugs. The current standard practice is to treat patients for as long as they continue to benefit, only stopping treatment if the patient’s cancer comes back, or if the side effects are too bad. Often treatment can go on for several years.

    This trial will compare the standard treatment duration with a shorter, fixed, treatment duration (1 year). The main aim is to find out if treatment can be stopped after 1 year, by assessing whether treating for 1 year is no worse than treating for longer than 1 year, in terms of the cancer coming back.
    E.2.2Secondary objectives of the trial
    The key secondary objective is to evaluate how the length of treatment affects patients’ quality of life (QoL), and determine whether shorter duration treatment achieves better QoL outcomes.

    Other secondary objectives are:
    • to determine whether overall survival (OS) and tumour response are no worse when using shorter duration therapy compared to standard duration
    • to compare safety and toxicity of the two treatment strategies
    • to evaluate the cost-effectiveness of the two treatment strategies
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Eligibility for REGISTRATION
    • Histologically or cytologically confirmed unresectable stage III or stage IV (metastatic) melanoma, including cutaneous and non-cutaneous melanoma
    • Aged ≥ 18 years
    • Planned or currently receiving (<12 months) treatment with first-line pembrolizumab or nivolumab
    • Written informed consent for registration

    Inclusion criteria for RANDOMISATION
    • Registered in DANTE
    • Progression-free by RECIST v1.1 criteria at 12 months (+/- 4 weeks) from the start of pembrolizumab or nivolumab
    • 12 months (+/- 4 weeks) from start of pembrolizumab or nivolumab
    • Eastern co-operative oncology group (ECOG) performance status 0-2
    • Considered fit by the treating clinician to continue to receive ongoing treatment with pembrolizumab or nivolumab
    • Written informed consent for randomisation
    E.4Principal exclusion criteria
    Exclusion criteria for RANDOMISATION
    • Severe co-morbidities, including severe auto-immune disease or pneumonitis
    • Active infection requiring systemic therapy
    • Known history of HIV, hepatitis B or C
    • 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
    • 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.
    • 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.
    • 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)
    • Untreated brain metastases that are symptomatic and/or require local intervention (surgery, radiosurgery, corticosteroid therapy) or other systemic therapy.
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome measure is progression-free survival (PFS), calculated from the date of randomisation to the date of documented evidence of first progression or death (from any cause), or the date last known to be alive and progression-free for patients without a PFS event. This is a non-inferiority outcome measure.

    A sensitivity analysis to the primary endpoint will assess time to progression, where deaths without documented evidence of progression will be considered a competing risk event.
    E.5.1.1Timepoint(s) of evaluation of this end point
    PFS will be formally assessed during stages 3-5 of the trial. Stage 3 (interim assessment of efficacy) analysis will occur when at least half the required number of participants have been randomised and have completed 12 months of trial follow-up, and the study is at least 30 months into recruitment. Stage 4 (primary assessment of efficacy) analysis will occur when all participants have completed 12 months of follow-up after randomisation, which is anticipated to be 6 years from the start of recruitment. Stage 5 (long-term assessment of efficacy) analysis will take place when all participants have completed 4 years of follow-up after randomisation.
    E.5.2Secondary end point(s)
    The key secondary outcome measure is Quality of Life (QoL) measured using the EORTC QLQ-C30 questionnaire and the melanoma-specific module QLQ-MEL38, and the EQ-5D-5L (EuroQol). The main QoL outcome of interest is the EORTC QLQ-C30 summary score. This is a superiority outcome measure.

    Other secondary endpoints are:

    • Overall survival (OS), 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. This is a non-inferiority outcome measure
    • Objective response rate, calculated as the proportion of patients achieving either a complete or partial response. This is a non-inferiority outcome measure
    • Best tumour response rate, calculated as the proportion of patients achieving each best response (complete response, partial response, stable disease or progressive disease). This is a non-inferiority outcome measure
    • Duration of response, calculated as the time from first tumour response (after randomisation) until disease progression. This is a non-inferiority outcome measure
    • Safety and anti-PD1 therapy-related toxicity. Toxicity will be recorded using CTCAE v4
    • Cost-effectiveness of the two treatment strategies
    E.5.2.1Timepoint(s) of evaluation of this end point
    All secondary endpoints will be formally assessed during stage 4 of the trial. In addition, the secondary endpoints of OS and toxicity will be analysed at stage 5. Stage 4 (primary assessment of efficacy) analysis will occur when all participants have completed 12 months of follow-up after randomisation, which is anticipated to be 6 years from the start of recruitment. Stage 5 (long-term assessment of efficacy) analysis will take place when all participants have completed 4 years of follow-up after randomisation.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned50
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the trial is defined as the date of the collection of the last participant data item.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years10
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years10
    E.8.9.2In all countries concerned by the trial months0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 725
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 483
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state1208
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 0
    F.4.2.2In the whole clinical trial 1208
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    At the end of the trial, participants randomised to continue to receive anti-PD1 therapy and who remain progression-free, will be able to remain on treatment for as long as they continue to benefit, which is in line with standard practice.

    For participants randomised to stop treatment at 12 months, if their disease progresses, they will be offered standard treatment as per local policy.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2017-12-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-18
    P. End of Trial
    P.End of Trial StatusGB - no longer in EU/EEA
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 02:09:18 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA