E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced or metastatic melanoma treated with nivolumab monotherapy in a 480 mg 4 weekly scheme (either from start or after combination therapy with ipilimumab), have a confirmed CR or PR, are at least 6 months on treatment and are willing to receive 3 reduced doses of 240 mg |
Patiënten met gevorderd of uitgezaaid melanoom, behandeld met nivolumab monotehrapie in een 4-wekelijks 480 mg schema, die een bevestigde CR of PR hebben, minimaal 6 maanden behandeling hebben gehad en bereid zijn om 3 gereduceerde nivolumab doseringen te ontvangen. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with advanced or metastatic melanoma treated with nivolumab monotherapy and have a durable response |
Patiënten met gevorderd of uitgezaaid melanoom, behandeld met nivolumab monotherapie en een duurzaam respons. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective is to demonstrate that the nivolumab steady-state level after 3 cycles with a reduced nivolumab dosage (240 mg every 4 weeks) is not lower than the nivolumab concentration 4 weeks after the first 480 mg dose. |
Aantonen dat de nivolumab steady-state spiegels na 3 kuren met een gereduceerde dosering (240 mg, 4 wekelijks) niet lager is dan de spiegel na de eerste kuur met 480 mg. |
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E.2.2 | Secondary objectives of the trial |
- Explore PD1 receptor occupancy in PBMCs - Safety of reduced nivolumab doses - Efficacy of reduced nivolumab doses - Pharmacokinetic profile of nivolumab - Cost effectiveness
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- PD1 receptor bezetting onderzoeken in PBMCs - Veiligheid van gereduceerde nivolumab doseringen - Effectiviteit van gereduceerde nivolumab doseringen - Pharmacokinetisch profiel van nivolumab - Kosten-effectiviteit |
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E.2.3 | Trial contains a sub-study | No |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
No sub-study |
Geen sub-studie |
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E.3 | Principal inclusion criteria |
1. Age ≥ 18 years 2. Advanced or metastatic melanoma 3. Current treatment with nivolumab for advanced or metastatic melanoma, in a 480 mg, 4 weekly scheme 4. Documented confirmed and ongoing CR or PR according to RECIST v1.1 5. On treatment for at least 6 months
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1. Leeftijd ≥ 18 jaar 2. Gevorderd of gemetastaseerd melanoom 3. Huidige behandeling met nivolumab voor gevorder of gemetastaseerd melanoom, in een 4 wekelijks 480 mg schema 4. Beschreven en bevestigd voortdurende CR of PR volgens RECIST v1.1 5. Minimaal 6 maanden op behandeling
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E.4 | Principal exclusion criteria |
- Unable to draw blood for study purposes - Patients willing to participate or already included in the SAFE-STOP trial
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- Niet mogelijk om bloed af te nemen - Patiënt wil of neemt reeds deel aan SAFE-STOP trial |
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E.5 End points |
E.5.1 | Primary end point(s) |
Difference between the mean trough level 4 weeks after the 3rd nivolumab dose of 240 mg and the mean trough level 4 weeks after treatment start (i.e. 4 weeks after the first 480 mg dose) |
Verschil tussen nivolumab dalspiegels op 4 weken na de 3de gereduceerde kuur van 240 mg met de dalspiegels na de 1ste kuur met 480 mg |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks after the 3rd reduced dose of 240 mg and 4 weeks after the 1st dose of 480 mg |
4 weken na 3de gereduceerde kuur van 240 mg en 4 weken na 1ste kuur van 480 mg |
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E.5.2 | Secondary end point(s) |
- PD-1 receptor occupancy in PBMCs, measured 4 weeks after 3 reduced nivolumab doses - Grade ≥3 adverse events during reduced doses - Number of patients with new PD during 3 reduced doses - Pharmacokinetic profile of nivolumab - Cost effectiveness
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- PD-1 receptor bezetting in PBMCs, gemeten 4 weken na de 3rde gereduceerde nivolumab dosering - Graad ≥3 bijwerkingen tijdens de gereduceerde kuren - Aantal patiënten met nieuwe PD tijdens de gereduceerde kuren - Pharmacokinetisch profiel van nivolumab - Kosten-effecitiviteit |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 weeks after the 3rd reduced dose of 240 mg |
4 weken na de 3de gereduceerde nivolumab dosering. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |