Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Immunomodulating Agents

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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

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.

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.

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.

Nivolumab + Placebo

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.

Nivolumab + Ipilimumab

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.

Double Placebo Control

Dirk Schadendorf, Prof. Dr.

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).

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.

Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab vs. Double Placebo for Stage IV Melanoma w. NED

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

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

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.

The OS of a patient is defined as the time from date of randomization until date of death.

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.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab vs. Double Placebo for Stage IV Melanoma w. NED	NCT02523313	Malignant Melan...	Nivolumab + Pla... Nivolumab + Ipi... Double Placebo ...	18 Years -	University Hospital, Essen
Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab vs. Double Placebo for Stage IV Melanoma w. NED	NCT02523313	Malignant Melan...	Nivolumab + Pla... Nivolumab + Ipi... Double Placebo ...	18 Years -	University Hospital, Essen

Spots Global Cancer Trial Database for nivolumab + placebo