- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT02523313
Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab vs. Double Placebo for Stage IV Melanoma w. NED
10 december 2021 uppdaterad av: Prof. Dr. med. Dirk Schadendorf
A Phase II Randomized, Double-Blind Trial of Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab Versus Double-Placebo Control as a Post-Surgical/Post-Radiation Treatment for Stage IV Melanoma With No Evidence of Disease
This is a prospective, double-blind placebo-controlled, multicenter, randomized phase II trial testing the adjuvant immunotherapy with Nivolumab plus Ipilimumab Placebo or Nivolumab plus Ipilimumab versus Double Placebo Control as a post-surgical/post-radiation treatment for stage IV melanoma with no evidence of disease (NED).
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
This study will allow for direct comparison of the clinical benefit provided by Nivolumab monotherapy or Nivolumab combined with Ipilimumab versus double placebo control.
Furthermore, it will also allow for direct comparison of the respective safety profiles of Nivolumab monotherapy or Nivolumab combined with Ipilimumab.
Nivolumab monotherapy was chosen as one of the experimental arms because of a favourable risk-benefit ratio assessed in the large Phase 1 study (MDX1106-03/CA209-003).
The combination of Nivolumab and Ipilimumab was chosen as an experimental arm because of the preliminary evidence from the Phase 1 study CA209-004 suggesting synergy between Nivolumab and Ipilimumab resulting in a higher frequency of patients with increased tumour burden reduction.
Evaluating both Nivolumab monotherapy and the combination of Nivolumab and Ipilimumab will provide clinical data allowing clinicians to select the appropriate treatment for each patient based on their individual risk-benefit ratio.
Studietyp
Interventionell
Inskrivning (Faktisk)
167
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Berlin, Tyskland, 10117
- Charite Berlin
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Buxtehude, Tyskland, 21614
- Elbe Klinikum Buxtehude
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Dresden, Tyskland, 01307
- Universitätsklinikum Dresden
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Erfurt, Tyskland, 99089
- Helios Klinikum Erfurt
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Essen, Tyskland, 45147
- Studienzentrum Hautklinik Universitätsklinikum Essen (AöR) Klinik für Dermatologie
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Gera, Tyskland, 07548
- SRH Wald-Klinikum Gera GmbH
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Hannover, Tyskland, 30625
- Medizinische Hochschule Hannover
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Heidelberg, Tyskland, 69120
- Universitätrsklinikum Heidelberg Dermatologie / NCT
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Heilbronn, Tyskland, 74078
- SLK Kliniken Heilbronn GmbH
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Kiel, Tyskland, 24105
- Universitäts-Hautklinik Kiel Klinik f. Dermatologie, Venerologie u. Allergologie
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Leipzig, Tyskland, 04103
- Universitätsklinikum Leipzig Klinik u. Poliklinik f. Dermatologie, Venerologie u. Allergologie
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Ludwigshafen, Tyskland, 67063
- Klinikum der Stadt Ludwigshafen
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Lübeck, Tyskland, 23538
- UKSH Campus Lübeck
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Mainz, Tyskland, 55131
- Universitätsklinikum Mainz Hautklinik und Polklinik
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Mannheim, Tyskland, 68167
- Klinik für Dermatologie, Venerologie und Allergologie UMM - Universitätsmedizin Mannheim
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Minden, Tyskland, 32429
- Johannes Wesling Klinikum Minden Hautklinik
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München, Tyskland, 80337
- Universitätsklinikum München (LMU)
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Münster, Tyskland, 48157
- Fachklinik Hornheide
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Regensburg, Tyskland, 93053
- Universitätsklinikum Regensburg
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Tübingen, Tyskland, 72076
- Universitätshautklinik Tübingen
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown primary site with no evidence of disease (NED) after surgery or radiation therapy (conducted within 8 weeks before enrolment)
- Signed written informed consent
- Known BRAF status
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
- Minimum life expectancy of five years excluding their melanoma diagnosis
- ECOG performance status of 0 or 1
- Tumor tissue from the resected site of disease must be provided for biomarker analyses. In order to be randomized a subject must have a PD-L 1 expression classification (positive (≥ 5% tumor cells expressing PD-L1) or negative (< 5% tumor cells expressing PD-L1)). If an insufficient amount of tumor tissue from the resected site is provided for analysis, acquisition of additional archived tumor tissue (block and/or slides) for the biomarker analyses is required.
- Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration
- Required laboratory values
- Negative pregnancy test for female subjects and effective contraception (Pearl-Index <1) for both male and female subjects if the risk of conception exists
Exclusion Criteria:
- History of primary uveal or mucosal melanoma
- Prior therapy with CTLA4 or PD1 antibodies
- The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
- Lack of availability for clinical follow-up assessments.
- Any immunosuppressive therapy given within the past 30 days prior to study drug administration (excluding physiologic steroid hormone replacement)
- Other malignancies within the past five years requiring treatment except basal or squamous skin carcinomas or carcinoma in situ of the cervix
- Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years
- Patients with serious intercurrent illness, requiring hospitalization.
- Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
- The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
- Known hypersensitivity reaction to any of the components of study treatment
- Pregnancy (absence to be confirmed by ß-HCG urinary test, minimum sensitivity 25IU/L or equivalent units of HCG)) or lactation period
- Women of childbearing potential (WOCBP): Refusal or inability to use effective means of contraception (Pearl-Index <1). WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (Pearl-Index <1). Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
- Known alcohol or drug abuse
- Participation in another clinical study and use of any investigational or non-registered product (drug or vaccine) within the 30 days before registration
- Significant disease or condition which, in the investigator's opinion, would exclude the patient from the study
- Legal incapacity or limited legal capacity
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Crossover tilldelning
- Maskning: Trippel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Aktiv komparator: Nivolumab + Placebo
Nivolumab (3 mg/kg) i.v.
every 2 weeks + Placebo instead of Ipilimumab on weeks 1, 4, 7 and 10 + Placebo instead of Nivolumab on weeks 4 and 10
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Nivolumab will be applied at a dose of 3 mg/kg given as IV infusion every 2 weeks for up to 1 year after initial dosing or until PD + Placebo instead of Ipilimumab on weeks 1, 4, 7 and 10 + Placebo instead of Nivolumab on weeks 4 and 10.
Andra namn:
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Experimentell: Nivolumab + Ipilimumab
Nivolumab (1 mg/kg) and Ipilimumab (3 mg/kg) i.v.
every 3 weeks for 4 doses.
Both study drugs are administered on the same day over the first 12 weeks + Placebo instead of Nivolumab on weeks 3, 5, 9 and 11.
After week 12: Nivolumab as maintenance and at a dose of 3 mg/kg IV every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
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Nivolumab (1 mg/kg) and Ipilimumab (3 mg/kg) will be applied as IV infusion every 3 weeks for 4 doses.
Both study drugs are to be administered on the same day over the first 12 weeks + Nivolumab-Placebo on weeks 3, 5, 9 and 11.
After week 12 Nivolumab is given as maintenance and will be applied at a dose of 3 mg/kg IV every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
Andra namn:
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Placebo-jämförare: Double Placebo Control
Placebo instead of Nivolumab and Placebo instead of Ipilimumab i.v.
every 3 weeks for 4 doses.
Both placebos are administered on the same day over the first 12 weeks + Placebo instead of Nivolumab on weeks 3, 5, 9 and 11.
After week 12 Placebo instead of Nivolumab as maintenance and applied as IV every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
|
Placebo instead of Nivolumab and Placebo instead of Ipilimumab will be applied as IV infusion every 3 weeks for 4 doses.
Both placebos are to be administered on the same day over the first 12 weeks + Placebo instead of Nivolumab on weeks 3, 5, 9 and 11.
After week 12 Placebo instead of Nivolumab is given as maintenance and will be applied intravenously every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Efficacy of adjuvant immunotherapy with Nivolumab alone or in combination with Ipilimumab (Recurrence-free survival)
Tidsram: 24 months after the last patient ended treatment
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Recurrence-free survival (RFS) defined as the time from date of randomization until the date of the first recurrence (local or distant metastasis), new primary melanoma or death from any cause, whichever occurs first.
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24 months after the last patient ended treatment
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Overall survival (OS)
Tidsram: 24 months after the last patient ended treatment
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The OS of a patient is defined as the time from date of randomization until date of death.
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24 months after the last patient ended treatment
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Time to recurrence (TTR)
Tidsram: 24 months after the last patient ended treatment
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The TTR of a patient is defined as the time from date of randomization until date of disease recurrence (local or distant metastasis) or melanoma-related death.
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24 months after the last patient ended treatment
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Progression/recurrence free survival 2 (PRFS2) for crossover patients of Arm C
Tidsram: 24 months after the last patient ended treatment
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The PRFS2 is defined as time from date of randomization until the date of first disease progression per RECIST 1.1 beyond the initial unresectable disease recurrence, the date of second recurrence in patients without evidence of disease after surgery of a resectable first recurrence or the date of death, whichever occurs first.
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24 months after the last patient ended treatment
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Andra resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Safety / Toxicity All adverse events ≥ Grade 3 according to CTCAE Version 4.0 criteria
Tidsram: until 90 days after discontinuation of dosing
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All adverse events ≥ Grade 3 according to CTCAE Version 4.0 criteria, that are related to the administration of the investigational agents will be assessed
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until 90 days after discontinuation of dosing
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Dirk Schadendorf, Prof. Dr., Studienzentrum Hautklinik Universitätsklinikum Essen Klinik f. Dermatologie
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Livingstone E, Zimmer L, Hassel JC, Fluck M, Eigentler TK, Loquai C, Haferkamp S, Gutzmer R, Meier F, Mohr P, Hauschild A, Schilling B, Menzer C, Kiecker F, Dippel E, Roesch A, Ziemer M, Conrad B, Korner S, Windemuth-Kieselbach C, Schwarz L, Garbe C, Becker JC, Schadendorf D; Dermatologic Cooperative Oncology Group. Adjuvant nivolumab plus ipilimumab or nivolumab alone versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): final results of a randomised, double-blind, phase 2 trial. Lancet. 2022 Oct 1;400(10358):1117-1129. doi: 10.1016/S0140-6736(22)01654-3. Epub 2022 Sep 10.
- Zimmer L, Livingstone E, Hassel JC, Fluck M, Eigentler T, Loquai C, Haferkamp S, Gutzmer R, Meier F, Mohr P, Hauschild A, Schilling B, Menzer C, Kieker F, Dippel E, Rosch A, Simon JC, Conrad B, Korner S, Windemuth-Kieselbach C, Schwarz L, Garbe C, Becker JC, Schadendorf D; Dermatologic Cooperative Oncology Group. Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020 May 16;395(10236):1558-1568. doi: 10.1016/S0140-6736(20)30417-7.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart (Faktisk)
2 september 2015
Primärt slutförande (Faktisk)
27 juni 2021
Avslutad studie (Faktisk)
27 juni 2021
Studieregistreringsdatum
Först inskickad
5 augusti 2015
Först inskickad som uppfyllde QC-kriterierna
11 augusti 2015
Första postat (Uppskatta)
14 augusti 2015
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
13 december 2021
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
10 december 2021
Senast verifierad
1 december 2021
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Neoplasmer efter histologisk typ
- Neoplasmer
- Neuroektodermala tumörer
- Neoplasmer, könsceller och embryonala
- Neoplasmer, nervvävnad
- Neuroendokrina tumörer
- Nevi och melanom
- Melanom
- Molekylära mekanismer för farmakologisk verkan
- Antineoplastiska medel
- Antineoplastiska medel, immunologiska
- Immune Checkpoint-hämmare
- Nivolumab
- Ipilimumab
Andra studie-ID-nummer
- IMMUNED
Plan för individuella deltagardata (IPD)
Planerar du att dela individuella deltagardata (IPD)?
NEJ
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
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