DANTE - A trial to assess the length of anti-PD1 therapy for metastatic melanoma

DANTE: A randomised phase III trial to evaluate the Duration of ANti-PD1 monoclonal antibody Treatment in patients with metastatic mElanoma - DANTE (Duration of Anti-PD1 therapy for melanoma)

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2017-002435-42-GB

Enrollment

1208

Registered

2018-05-17

Start date

2018-01-18

Completion date

Unknown

Last updated

2018-05-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Advanced (unresectable stage III or stage IV (metastatic)) melanoma MedDRA version: 20.0 Level: PT Classification code 10025670 Term: Malignant melanoma stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classificat

Interventions

Product Name: Pembrolizumab Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: Pembrolizumab CAS Number: 1374853-91-4 Concentration unit: mg/kg milligram(s)/kil

Eligibility

Sex/Gender

All

Inclusion criteria

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 (=65 years) yes F.1.3.1 Number of subjects for this age range 483

Exclusion criteria

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.

Design outcomes

Primary

Measure	Time frame
Main Objective: 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. ;Secondary Objective: 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 ;Primary 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.;Timepoint(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	—

Measure

Time frame

Main Objective: 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. ;Secondary Objective: 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 ;Primary 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.;Timepoint(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

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Secondary

Measure	Time frame
Secondary 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;Timepoint(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.	—

Measure

Time frame

Secondary 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;Timepoint(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.

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Countries

United Kingdom

Contacts

Public ContactDr Sue Bell

Clinical Trials Research Unit (CTRU), University of Leeds

s.e.bell@leeds.ac.uk01133431492

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026