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Advanced Non Small Cell Lung CancerPhase 3eNERGYNCT03351361

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

A Phase 3 study testing Nivolumab + Ipilimumab and Chemotherapy in people with Advanced Non Small Cell Lung Cancer, run by Rennes University Hospital at 30 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Non Small Cell Lung Cancer
What is being tested?
Nivolumab + Ipilimumab and Chemotherapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
217 participants
Where
30 sitesFrance
Study dates
19 Feb 2018to 31 Jul 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent
  • Cytologically or histologically proven NSCLC (adenocarcinoma, squamous cell carcinoma, large-cell carcinoma)
  • Stage IV or non-treatable by radiotherapy or surgery stage III (7th classification)
  • No previous systemic chemotherapy for lung cancer, except in case of relapse after adjuvant treatment for localized disease with 6 months or more between end of previous chemotherapy and relapse
  • Patients less than 70 years old and PS 2 or 70 years older PS 0 to 2
  • Judged fit enough to receive a carboplatin based doublet according to ESMO guidelines
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  • Presence of at least one measurable target lesion (RECIST 1.1 rules) in a non-irradiated region and analysable by CT
  • Life expectancy superior at 12 weeks
  • Prior radiation therapy is authorized if it involved less than 25% of the total bone marrow volume and finished 14 days before D1 of planned treatment
  • Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization/registration WBC superior or equal at at 2000/μL Neutrophils superior or equal at at 1500/μL Platelets superior or equal at at 100 x103/μL Hemoglobin superior at 10.0 g/dL Serum creatinine inferior or equal at 1.5 x ULN or creatinine clearance (CrCl) superior or equal at at 45 mL/min (if using the Cockcroft-Gault formula ) AST/ALT inferior or equal at 3 x ULN Total Bilirubin inferior or equal at 1.5 x ULN (except Patients with Gilbert Syndrome, who can have total bilirubin inferior at 3.0 mg/dL)
  • Availability of adequate FFPE tumor-derived material (tumor blocks or slides) from a biopsy, surgery or fine needle aspirate for analysis of PD-L1 testing by IHC
  • Age and Reproductive Status
  • Women of childbearing potential (WOCBP) must use appropriate method(s) of contraception during treatment.
  • WOCBP should use an adequate method to avoid pregnancy :
  • For 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of nivolumab + ipilimumab,
  • For 4 weeks after the last dose of carboplatine + pemetrexed,
  • For 5 weeks after the last dose of carboplatine + paclitaxel.
  • Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to the start of treatment
  • Women must not be breastfeeding
  • Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year during treatment Men will be instructed to adhere to contraception for a period of 31 weeks after the last dose of nivolumab + ipilimumab and with carboplatine +pemetrexed or carboplatine + paclitaxel up to 6 months thereafter.

Who cannot join

  • Patients with other severe concurrent disorders that occurred during the prior six months before enrollment (myocardial infection, severe or unstable angor, coronarian or peripheric arterial bypass operation, NYHA class 3 or 4 congestive heart failure, transient or constituted cerebral ischemic attack, at least grade 2 peripheral neuropathy, psychiatric or neurological disorders preventing the patient from understanding the trial, uncontrolled infections) are not eligible.
  • Serious or uncontrolled systemic disease judged as incompatible with the protocol by the investigator
  • Another previous or concomitant cancer, except for basocellular cancer of the skin or treated cervical cancer in situ, or appropriately treated localized low-grade prostate cancer (Gleason score inferior at 6), unless the initial tumor was diagnosed and definitively treated more than 5 years previously, with no evidence of relapse.
  • Known activating mutation of EGFR (del LREA exon 19, mutation L858R or L861X of exon 21, mutation G719A/S in exon 18) or EML4-ALK or ROS-1 translocation
  • Superior at caval syndrome
  • Uncontrolled infectious status
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  • All concurrent radiotherapy
  • Concurrent administration of one or several other anti-tumor therapies.
  • Psychological, familial, social or geographic difficulties preventing follow-up as defined by the protocol.
  • Protected person (adults legally protected (under judicial protection, guardianship or supervision), person deprived of their liberty, pregnant woman, lactating woman and minor),
  • Concurrent participation in another clinical trial
  • Patients are excluded if they have active brain metastases or leptomeningeal metastases. Patients with brain metastases are eligible if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for [lowest minimum is 4 weeks or more] after treatment is complete and within 28 days prior to the first dose of nivolumab and ipilimumab administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (superior at 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration.
  • Patients should be excluded if they have an active, known or suspected autoimmune disease. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
  • Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (superior at 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses superior at 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • Patients should be excluded if they have a lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity
  • Allergies and Adverse Drug Reaction
  • History of allergy to study drug components
  • Severe spinal hypoplasia and / or hemorrhagic tumors

Trial locations and contacts

30 sites in 1 country.

30 sites in 1 country

France30 sites

  • CH du Pays d'Aix

    Aix-en-Provence

  • CHU d'Angers

    Angers

  • CH de Beauvais

    Beauvais

  • CHU de Brest

    Brest

  • Centre Francois Baclesse

    Caen

  • CH René Dubos

    Cergy-Pontoise

  • CH de Charleville-Mézières

    Charleville-Mézières

  • HIA Percy

    Clamart

  • CH Intercommunal

    Créteil

  • CH Intercommunal des Alpes du Sud

    Gap

  • CH Départemental Vendée

    La Roche-sur-Yon

  • CH de Versailles

    Le Chesnay

  • CH Robert Boulin

    Libourne

  • CHU de Limoges

    Limoges

  • CH de Bretagne Sud

    Lorient

  • Centre Léon Bérard

    Lyon

  • CH François Quesnay

    Mantes-la-Jolie

  • APHM Hôpital Nord

    Marseille

  • Hôpital Européen

    Marseille

  • Institut Paoli-Calmette

    Marseille

  • CH de Meaux

    Meaux

  • CH de la Région d'Annecy

    Pringy

  • CHU de Rennes

    Rennes

  • CHU de Rouen

    Rouen

  • CH de Saint-Brieuc

    Saint-Brieuc

  • CHU de Saint-Etienne

    Saint-Priest-en-Jarez

  • CLCC Paul Strauss

    Strasbourg

  • CH Intercommunal Toulon-La Seyne-sur-Mer

    Toulon

  • HIA Saint-Anne

    Toulon

  • CH de Villefranche sur Saône

    Villefranche-sur-Saône

Other trials in France

About this study

Official title: 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

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.

Read more

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.

Being tested
Nivolumab + Ipilimumab, Chemotherapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nivolumab + IpilimumabDrug

    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.

  • ChemotherapyDrug

    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.

Study groups in NCT03351361
Study groupRoleWhat they receive
Nivolumab + IpilimumabExperimentalNot described
Receives: Drug: Nivolumab + Ipilimumab
ChemotherapyActive comparatorcarboplatin and pemetrexed or carboplatin and paclitaxel
Receives: Drug: Chemotherapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall survival

    Measured: From date of randomization until the date of date of death from any cause, whichever came first, assessed up to 3 years maximum

Secondary outcomes (9)

  1. Survival rate

    Measured: 1 year

  2. Objective response rate

    according to RECIST 1.1

    Measured: 2 years

  3. Progression free survival

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximum

  4. Safety rate

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

    Measured: 2 years

  5. Tolerability rate

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

    Measured: 2 years

  6. Quality of life score

    according to EQ-5D questionnaire

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximum

  7. Quality of life score

    according to EORTC QLQ-ELD14 questionnaire

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years maximum

  8. PD-L1

    testing by immunochemistry

    Measured: 2 years

  9. Geriatric evaluation

    according to geriatric mini data set

    Measured: inclusion and 2 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2017
  2. Study start19 Feb 2018
  3. Primary completion31 Jul 2021
  4. Study completion31 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
217 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03351361
Sponsor's protocol ID
2017-002842-60
Other IDs
35RC16_9734, 08-2015, CA209-449, 2017
Acronym
eNERGY
Status last verified
Feb 2023
First submitted
14 Nov 2017
Last updated
1 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lena H, Greillier L, Cropet C, Bylicki O, Monnet I, Audigier-Valette C, Falchero L, Vergnenegre A, Demontrond P, Geier M, Guisier F, Hominal S, Locher C, Corre R, Chouaid C, Ricordel C; GFPC 08-2015 ENERGY investigators. Nivolumab plus ipilimumab versus carboplatin-based doublet as first-line treatment for patients with advanced non-small-cell lung cancer aged >/=70 years or with an ECOG performance status of 2 (GFPC 08-2015 ENERGY): a randomised, open-label, phase 3 study. Lancet Respir Med. 2025 Feb;13(2):141-152. doi: 10.1016/S2213-2600(24)00264-9. Epub 2024 Oct 29.

    PubMed 39486424

  • Gijtenbeek RG, de Jong K, Venmans BJ, van Vollenhoven FH, Ten Brinke A, Van der Wekken AJ, van Geffen WH. Best first-line therapy for people with advanced non-small cell lung cancer, performance status 2 without a targetable mutation or with an unknown mutation status. Cochrane Database Syst Rev. 2023 Jul 7;7(7):CD013382. doi: 10.1002/14651858.CD013382.pub2.

    PubMed 37419867

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Nivolumab + Ipilimumab and Chemotherapy in people with Advanced Non Small Cell Lung Cancer, run by Rennes University Hospital at 30 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall survival (time frame: From date of randomization until the date of date of death from any cause, whichever came first, assessed up to 3 years maximum). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03351361, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Mar 2023.

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