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AzTrials

Non-Small Cell Lung Cancer MetastaticPhase 3DICIPLENCT03469960

Double Immune Checkpoint Inhibitors in PD-L1-positive Stage IV Non-small Lung CancEr

A Phase 3 study testing Ipilimumab and Nivolumab in people with Non-Small Cell Lung Cancer Metastatic, run by Intergroupe Francophone de Cancerologie Thoracique at 47 sites in France.

Completed

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

Official record
Search all trials

Trial summary

Non Small Cell lung cancer (NSCLC) remains the first cause of death by cancer in the World. For the patients presenting a NSCLC stage IV, the median of survival is about 15 months today. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Non-Small Cell Lung Cancer Metastatic
What is being tested?
Ipilimumab and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
265 participants
Where
47 sitesFrance
Study dates
2 May 2018to 15 Oct 2025
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed Written Informed Consent:
  • Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
  • Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
  • Histologically-proven NSCLC (squamous or non-squamous)
  • Stage IV (M1, including M1a pleural involvement) disease (8th classification TNM, UICC 2015)
  • ECOG PS < 1
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  • Weight loss< 10% in previous 3 months
  • No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease.
  • Age≥ 18 years, <75 years
  • Life expectancy > 3 months
  • Measurable tumor disease by CT or MRI per RECIST 1.1 criteria
  • Available tumor samples for centralized PD-L1 immunohistochemistry analysis
  • PD-L1 tumor content ≥ 1% and < 50% tumor cells as assessed locally by the investigator center
  • Adequate biological functions:
  • Creatinine Clearance ≥ 50 mL/min (Cockcroft or MDRD or CKD-epi); neutrophiles ≥ 1500/mm3 ; platelets ≥100 000/mm3 ; Hemoglobin ≥ 9g/dL ; hepatic enzymes < 3x ULN, total bilirubin ≤ 1,5 x ULN except for patients with proved, Gilbert syndrome (≤ 5 x ULN) or patients with hepatic metastases (≤ 3,0 mg/dL)
  • Women of childbearing potential (WOCBP) and sexually active should use an efficacious contraception method within the 28 days preceding the first dose and during the 6 months following the last dose of treatment. Women 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 study drug.
  • For Male subjects who are sexually active with WOCBP, an efficacious contraception method should be used during the treatment and during the 7 months following the last dose.
  • Investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception. Highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly. At a minimum, subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective.
  • Patient inclusion validated by a multidisciplinary meeting.

Who cannot join

  • Small cell lung cancer or tumors with mixt histology including a SCLC component
  • Known EGFR activating tumor mutation (deletion LREA in exon 19, L858R ou L861X mutations in exon 21, G719A/S mutation in exon 18) or HER exon 20 insertion (either tissue or plasma cfDNA mutation).
  • Known ALK or ROS1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS sequencing
  • Previous or active cancer within the previous 5 years (except for treated carcinoma in situ of the cervix or basal cell skin cancer). Patients with a prostate adenocarcinoma history within the previous 5 years could be included in case of localized prostate cancer, with good prognostic factors according to d'Amico classification (≤ T2a and Score de Gleason ≤ 6 and PSA (ng/ml) ≤ 10), provided they were treated in a curative way (surgery or radiotherapy, without any chemotherapy)
  • Superior vena cava (SVC) syndrome persisting after SVC stenting
  • Thoracic radiotherapy needed at initiation of tumor treatment, except bone palliative radiotherapy on a painful or compressive metastasis, respecting 4 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment
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  • Symptomatic untreated brain metastasis (without previous whole brain radiotherapy or stereotactic ablative brain radiotherapy or without surgical resection). At least 4 weeks delay between the end of radiotherapy and the beginning of induction immunotherapy treatment should be respected. Asymptomatic brain metastasis, not needing corticosteroids greater than 10 mg prednisone equivalent daily or mannitol infusions, with no evolution on brain MRI or CT-scan within the previous month are allowed.
  • History of previous primary immunodeficiency, organ transplantation needing an immunosuppressive treatment, any immunosuppressive drug within 28 days before randomization date, or history of severe toxicity (grade 3/4) by immune mechanism linked to another immunotherapy treatment.
  • Systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the immunotherapy induction. Inhaled, nasal or topic corticosteroids are allowed.
  • History of active autoimmune disease including rheumatoid polyarthritis, Lupus, Wegener disease. Patients with type I diabetes, or hypothyroidism, or immune cutaneous disease (vitiligo, psoriasis, alopecia) not needing any immunosuppressive systemic treatment, are allowed to be included.
  • Active inflammatory intestinal disease (diverticulosis, Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea
  • Active uncontrolled infection including tuberculosis, known acute viral hepatitis B and C according to serological tests. Patients with serological sequelae of cured viral hepatitis are allowed to be included.
  • HIV known infection
  • Living attenuated vaccine received within the 30 previous days
  • Previous treatment with anti-PD-1, anti-PD-L1 or Anti-CTLA4 antibody
  • Previous treatment with chemotherapy
  • General serious condition such as congestive uncontrolled cardiac failure, uncontrolled cardiac arrythmia, uncontrolled ischemic cardiac disease (unstable angina or history of myocardial infarction in the previous 6 months), history or stroke within the 6 previous months
  • Pre-existing lung interstitial disease as assessed by the diagnosis CT-scan.

Trial locations and contacts

47 sites in 1 country.

47 sites in 1 country

France47 sites

  • Amiens - CHU

    Amiens

  • Angers - CHU

    Angers, 49000

  • Annecy - CH

    Annecy, 74374

  • Argenteuil -CH

    Argenteuil, 95100

  • Avignon - CH

    Avignon

  • Bordeaux - Polyclinique Nord

    Bordeaux

  • Boulogne - Ambroise Paré

    Boulogne-Billancourt

  • Caen - CHU Côte de Nacre

    Caen, 14000

  • Cahors - CH

    Cahors, 46000

  • CH de Pontoise

    Cergy-Pontoise

  • CH Chambery

    Chambéry

  • CH de Chauny

    Chauny

  • CH

    Cholet

  • Clamart - Hôpital Percy

    Clamart, 92140

  • Clermont Ferrand - CHU

    Clermont-Ferrand, 63000

  • Colmar - CH

    Colmar, 68000

  • Dijon - CAC

    Dijon, 21000

  • CHRU Grenoble

    Grenoble

  • La Roche Sur Yon - CH

    La Roche-sur-Yon, 85925

  • Centre Hospitalier - Pneumologie

    Le Mans, 72000

  • CHRU de Lille

    Lille

  • CHU de Limoges

    Limoges

  • CH Lyon Sud - Pneumologie

    Lyon

  • Institut Paoli Calmette

    Marseille

  • Marseille - Hôpital Européen

    Marseille

  • Mont de Marsan - CH

    Mont-de-Marsan, 40000

  • Mulhouse - CH

    Mulhouse, 68000

  • Nantes - Centre René Gauducheau

    Nantes, 44805

  • Centre Antoine Lacassagne

    Nice

  • CHU Nîmes

    Nîmes

  • Orléans - CH

    Orléans, 45000

  • AP-HP Hopital Tenon - Pneumologie

    Paris, 75020

  • AP-HP Hôpital Bichat

    Paris

  • GH Paris Saint-Joseph

    Paris

  • Hôpital Saint Louis APHP

    Paris

  • Paris - Institut Curie

    Paris

  • Rouen - CHU

    Rouen, 76000

  • Centre René Huguenin

    Saint-Cloud

  • HIA Begin

    Saint-Mandé

  • ICL Lucien Neuwirth

    Saint-Priest-en-Jarez

  • Saint Quentin - CH

    Saint-Quentin, 02100

  • Suresnes - Hopital Foch

    Suresnes, 92151

  • Toulon - CHI

    Toulon, 83000

  • CHU Toulouse

    Toulouse

  • CHRU de Tours

    Tours

  • Versailles - CH

    Versailles, 78157

  • CH de Villefranche - Pneumologie

    Villefranche

Other trials in France

About this study

Official title: A Randomized Phase 3 Trial Comparing Continuation Nivolumab-Ipilimumab Doublet Immunotherapy Until Progression Versus Observation in Treatment-naive Patients With PDL1-positive Stage IV Non-Small Cell Lung Cancer (NSCLC) After Nivolumab-Ipilimumab Induction Treatment

Non Small Cell lung cancer (NSCLC) remains the first cause of death by cancer in the World. For the patients presenting a NSCLC stage IV, the median of survival is about 15 months today. The chemotherapy with platinum is the standard treatment for these patients but immunotherapy showed these efficacy in 1st line for patients PD-L1 positive. On the other hand, the duration of treatment by immunotherapy is not clear. Indeed, prolonged responses and long survivals have been described in patients having interrupted the treatment. In the melanoma, a treatment of 6 months of ipilimumab demonstrated its efficacy. The objective of the study is to demonstrate that a treatment of 6 months followed by an observation (stop and go) is not less effective than a treatment given until progression or toxicity. This strategy would allow to decrease the accumulated toxicities, to improve the quality of life of the patients and to decrease the costs.

Being tested
Ipilimumab, Nivolumab
Keywords
IFCT, DICIPLE, NSCLC

What participants receive

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

Study groups in NCT03469960
Study groupRoleWhat they receive
Arm A : standard treatmentActive comparator6 months of treatment by nivolumab + ipilimumab then nivolumab + ipilimumab then in case of progression platinum-based doublet recommended
Receives: Drug: Ipilimumab; Drug: Nivolumab
Arm B : experimental armExperimental6 months of treatment by nivolumab + ipilimumab then observation the in case of progression nivolumab + ipilimumab then in case of progression platinum-based doublet recommended
Receives: Drug: Ipilimumab; Drug: Nivolumab

What is being measured

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

  1. Progression Free Survival (PFS1)

    Time between the date of randomization and the first date of documented progression, as determined by BICR (Blinded Independent Central Review), or death due to any cause, whichever occurs first.

    Measured: 24 months after randomization of the last subject

Secondary outcomes (9)

  1. Progression Free Survival (PFS2)

    Time between the start date of the second line and the second date of documented progression, as determined by BICR, or death due to any cause, whichever occurs first.

    Measured: 24 months after randomization of the last subject

  2. Quality of life (QoL)

    Time until definitive deterioration (TUDD) from the randomization time in the experimental arm B.

    Measured: 24 months after randomization of the last subject

  3. Overall survival (OS)

    Measured: 6, 12 and 18 months after randomization

  4. Biological correlative exploratory studies (PD-L1)

    PD-L1-stained % of tumor cells will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

    Measured: 6 months

  5. Biological correlative exploratory studies (PD-L1 H score)

    PD-L1 H-score will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

    Measured: 6 months

  6. Biological correlative exploratory studies (CD3/CD8)

    CD3/CD8 tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

    Measured: 6 months

  7. Biological correlative exploratory studies (neutrophil)

    neutrophil tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

    Measured: 6 months

  8. Biological correlative exploratory studies (cytokines)

    plasma concentration of different cytokines at baseline or at the randomization point, will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

    Measured: 6 months

  9. Biological correlative exploratory studies (chemokines)

    plasma concentration of different chemokines at baseline or at the randomization point, will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

    Measured: 6 months

Timeline

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

  1. First posted19 Mar 2018
  2. Study start2 May 2018
  3. Primary completion8 Nov 2023
  4. Study completion15 Oct 2025

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
265 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03469960
Sponsor's protocol ID
IFCT-1701
Other IDs
2017-002540-33, 2017
Acronym
DICIPLE
Status last verified
Nov 2025
First submitted
16 Feb 2018
Last updated
18 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: The individual participant data underlying the results reported in this article, as well as the study protocol and statistical analysis plan, will be made available after deidentification immediately following publication and for three years. Researchers who provide a methodologically sound proposal for any purpose may direct proposals to contact@ifct.fr. To gain access, data requestors will need to sign a data access agreement that requires approval by the French Cooperative Thoracic Intergroup.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ipilimumab and Nivolumab in people with Non-Small Cell Lung Cancer Metastatic, run by Intergroupe Francophone de Cancerologie Thoracique at 47 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 19 inclusion and 18 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 18 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 47 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?

Progression Free Survival (PFS1) (time frame: 24 months after randomization of the last subject). 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 NCT03469960.

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 18 Nov 2025.

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