Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Pemetrexed

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

carboplatin and pemetrexed or carboplatin and paclitaxel

Nivolumab dosed intravenously over 30 minutes at 240 mg every 2 weeks combined with Ipilimumab dosed intravenously over 30 minutes at 1 mg/kg every 6 weeks until disease progression, unacceptable toxicity, or other reasons specified in the protocol.

Nivolumab + Ipilimumab

Doublet of chemotherapy according to standard of care carboplatin (AUC 5) with a dose that will be capped to 700 mg and pemetrexed (500 mg/m²) over 4 to 6 hours every three weeks (restricted to non-squamous histology) or carboplatin (AUC 6) with a dose that will be capped to 700 mg and paclitaxel (90 mg/m²) D1 D8 D15 over 4 to 6 hours every 4 weeks, with a maximum of 4 cycles of carboplatin based doublet, and the possibility to use maintenance with pemetrexed.

Chemotherapy

Hervé Léna

Lung cancer is the most common cancer in the world and the leading cause of cancer-related deaths in Western countries. Unfortunately, at the time of diagnosis, the majority of patients already have metastatic disease and a systemic, palliative treatment is the primary therapeutic option.

Guidelines for PS 2 patients or older than 75 years old patients at the time of diagnosis recommend for fit patients a carboplatin doublet chemotherapy.

Nivolumab has proven efficacy in 3rd line squamous cell lung carcinoma and is superior to chemotherapy in 2nd line treatment of squamous and non-squamous lung cancer in term of overall survival.

In 1st line, nivolumab failed to show superiority compared to a platin based doublet in terms of progression free survival and overall survival in tumors ≥ 5% PD-L1 expression. The association Nivolumab plus Ipilimumab showed encouraging results in first line setting in phase 1 study.

The investigators think that with regard to the manageable toxicity of nivolumab in lung cancer population and the possibility to obtain long responses, this association could be a valid option for this population of elderly and/or PS2 patients in term of overall survival.

Nivolumab and Ipilimumab Versus Chimiotherapy in First Line Treatment in PS 2 or Elderly in Advanced NSCLC Patients

Randomized Phase III Study Testing Nivolumab and Ipilimumab Versus a Carboplatin Based Doublet in First Line Treatment of PS 2 or Elderly (More Than 70 Years Old) Patients With Advanced Non-small Cell Lung Cancer

Incidence of Treatment-Emergent Adverse Events according to CTCAE version 4.0

according to EORTC QLQ-ELD14 questionnaire

Rennes University Hospital

Skin and Connective Tissue Diseases

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

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

Immunomodulating Agents

nivolumab 3 mg/kg q3w + ipilimumab 1 mg/kg q3w for 4 injections followed by nivolumab 480 mg IV q4w until completion of 2 years total treatment or progression. Then treatment will be left at the investigator choice and continued until the 2nd progression.

encorafenib 450 mg QD + binimetinib 45 mg BID orally for 12 weeks followed, after a week of pause, by nivolumab 3 mg/kg q3w + ipilimumab 1 mg/kg q3w for 4 injections, followed by nivolumab 480 mg IV q4w until completion of 2 years total treatment or progression. Then patients will be rechallenged with encorafenib 450 mg QD + binimetinib 45 mg BID orally continuously until the 2nd progression.

nivolumab 3 mg/kg q3w + ipilimumab 1 mg/kg q3w for 4 injections followed by nivolumab 480 mg IV q4w until completion of 2 years total treatment or progression.

encorafenib 450 mg QD + binimetinib 45 mg BID orally for 12 weeks

Encorafenib + Binimetinib

Caroline Robert

This is a multicenter, 2-arm open-label, randomized comparative phase II study. The objective of this trial is to prospectively evaluate whether a sequential approach with an induction period of 12 weeks with encorafenib + binimetinib followed by combination immunotherapy with nivolumab + ipilimumab improves progression free survival compared to combination immunotherapy nivolumab + ipilimumab alone in patients with BRAF V600 mutation-positive unresectable or metastatic melanoma.

Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib

Combination of Targeted Therapy (Encorafenib and Binimetinib) Followed by Combination of Immunotherapy (Ipilimumab and Nivolumab) vs Immediate Combination of Immunotherapy in Patients With Unresectable or Metastatic Melanoma With BRAF V600 Mutation : an EORTC Randomized Phase II Study (EBIN)

All publications must comply with the terms specified in the EORTC Policy 009 "Release of Results and Publication Policy".

PRS is defined as the time from the date of randomization until the first date of progression, or until date of death (whatever the cause), whichever occurs first. Progression will be assessed according to the RECIST criteria (version 1.1)

OS is defined as the time from the date of randomization to the date of death, whatever the cause.

CR will be assessed according to the RECIST criteria (version 1.1)

Time to CR is defined as the time from the date of randomization until the occurrence of first CR.

Duration of CR will be measured from the time measurement criteria for CR are first met until the first date that recurrence is objectively documented.

Best overall response will be assessed according to the RECIST criteria (version 1.1)

Time to best response is defined as the time from the date of randomization until the occurrence of the best response (CR or PR, whichever comes first). CR and PR will be assessed according to the RECIST criteria (version 1.1)

Best response duration will be measured from the time measurement criteria for CR/PR (whichever is first recorded) are first met until the first date that recurrent or progressive disease is objectively documented. CR and PR will be assessed according to the RECIST criteria (version 1.1)

This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, for adverse event reporting.

PFS2 is defined as the time from randomization to second objective disease progression, or death from any cause, whichever first. The second objective disease progression will be assessed according to the RECIST criteria (version 1.1)

European Organisation for Research and Treatment of Cancer - EORTC

Nivolumab + Ipilimumab alone (standard dosage regimen)

SBRT (recommended optimal dose) with Nivolumab + Ipilimumab (standard dosage regimen)

Combined treatment schema

This study is a phase I/II, multicenter, open-label study starting with a phase I part followed by a Phase II part.

The phase I part of the study aims at evaluating the safety and efficacy (in terms of abscopal effect at week 6) of the treatment combination schema of Stereotactic Body Radiation Therapy (SBRT) and PD-1 plus CTLA-4 inhibitors in patients with metastatic melanoma. Patients will be assigned in one of 3 cohorts depending the metastatic site. 18 patients will be enrolled in each cohort.

Once the recommended optimal radiotherapy dose has been declared for the 3 cohorts, patients will be enrolled in the phase II part of the study in order to evaluate the activity (progression-free survival at 6 months) of SBRT given in combination with immune checkpoints inhibitors in patients with metastatic melanoma.

66 patients will be included in the phase II.

Induction of Immune-mediated aBscOpal Effect thrOugh STEreotactic Radiation Therapy in Metastatic Melanoma Patients Treated by PD-1 + CTLA-4 Inhibitors (BOOSTER MELANOMA)

Abscopal effect is defined as a tumor shrinkage ≥ 20% compared to baseline in the control lesion (non-irradiated and distant lesion) at the end of the 6-week period of treatment without evidence of clinical progression.

Institut Claudius Regaud

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.

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.

Prof. Dr. med. Dirk Schadendorf

Prof. Dr. med.

Mesothelioma

Mesothelioma, Malignant

Adenoma

Neoplasms, Glandular and Epithelial

Neoplasms, Mesothelial

Pleural Neoplasms

Malignant Mesothelioma

Nivolumab administered IV over 60 minutes at 3mg/kg every 2 weeks

Nivolumab administered IV over 60 minutes at 3mg/kg every 2 weeks, combined with Ipilimumab administered IV over 90 minutes at 1mg/Kg every 6 weeks

Arnaud Scherpereel, MD, PhD

Gérard Zalcman, MD, PhD

The sponsor raise the hypothesis that inhibition of immune PD-1+/- CTLA-4 check-point(s) would delay tumor progression in patients with unresectable MPM, experiencing disease progression after one or two lines of chemotherapy including at least first-line with pemetrexed and platinum, without altering significantly the quality of life of patients.

Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients

A Randomized Phase II Study Evaluating Efficacy and Safety of 2nd or 3rd Line Treatment by Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients

Tumor assessment (modified RECIST1.0 for mesothelioma)

LCSS ( Lawrence County School System) Scale

dosage in blood of numerous biomarkers and analysis of their prognosis impact

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Nivolumab and Ipilimumab Versus Chimiotherapy in First Line Treatment in PS 2 or Elderly in Advanced NSCLC Patients	NCT03351361	Advanced Non Sm...	Nivolumab + Ipi... Chemotherapy	18 Years -	Rennes University Hospital
Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib	NCT03235245	Unresectable St... Stage IV Melano...	Nivolumab + Ipi... Encorafenib + B...	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Nivolumab and Ipilimumab Versus Chimiotherapy in First Line Treatment in PS 2 or Elderly in Advanced NSCLC Patients	NCT03351361	Advanced Non Sm...	Nivolumab + Ipi... Chemotherapy	18 Years -	Rennes University Hospital
Induction of Immune-mediated aBscOpal Effect thrOugh STEreotactic Radiation Therapy in Metastatic Melanoma Patients Treated by PD-1 + CTLA-4 Inhibitors (BOOSTER MELANOMA)	NCT03354962	Melanoma	Nivolumab + Ipi... Combined treatm...	18 Years -	Institut Claudius Regaud
Induction of Immune-mediated aBscOpal Effect thrOugh STEreotactic Radiation Therapy in Metastatic Melanoma Patients Treated by PD-1 + CTLA-4 Inhibitors (BOOSTER MELANOMA)	NCT03354962	Melanoma	Nivolumab + Ipi... Combined treatm...	18 Years -	Institut Claudius Regaud
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
Nivolumab Monotherapy or Nivolumab Plus Ipilimumab, for Unresectable Malignant Pleural Mesothelioma (MPM) Patients	NCT02716272	Mesothelioma	Nivolumab Nivolumab + Ipi...	18 Years -	Intergroupe Francophone de Cancerologie Thoracique
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 + ipilimumab