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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03469960
Recruitment Status : Recruiting
First Posted : March 19, 2018
Last Update Posted : September 4, 2019
Sponsor:
Information provided by (Responsible Party):
Intergroupe Francophone de Cancerologie Thoracique

Brief 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. 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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Metastatic Drug: Ipilimumab Drug: Nivolumab Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Active Comparator: Arm A : standard treatment
6 months of treatment by nivolumab + ipilimumab then nivolumab + ipilimumab then in case of progression platinum-based doublet recommended
Drug: Ipilimumab
Ipilimumab 1 mg/kg every 6 weeks

Drug: Nivolumab
Nivolumab 3 mg/kg every 2 weeks

Experimental: Arm B : experimental arm
6 months of treatment by nivolumab + ipilimumab then observation the in case of progression nivolumab + ipilimumab then in case of progression platinum-based doublet recommended
Drug: Ipilimumab
Ipilimumab 1 mg/kg every 6 weeks

Drug: Nivolumab
Nivolumab 3 mg/kg every 2 weeks




Primary Outcome Measures :
  1. Progression Free Survival (PFS1) [ Time Frame: 24 months after randomization of the last subject ]
    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.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS2) [ Time Frame: 24 months after randomization of the last subject ]
    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.

  2. Quality of life [ Time Frame: 24 months after randomization of the last subject ]
    Time until definitive deterioration (TUDD) from the randomization time in the experimental arm B.

  3. Overall survival (OS) [ Time Frame: 6, 12 and 18 months after randomization ]
  4. Biological correlative exploratory studies (PD-L1) [ Time Frame: 6 months ]
    PD-L1-stained % of tumor cells will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

  5. Biological correlative exploratory studies (PD-L1 H score) [ Time Frame: 6 months ]
    PD-L1 H-score will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

  6. Biological correlative exploratory studies (CD3/CD8) [ Time Frame: 6 months ]
    CD3/CD8 tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

  7. Biological correlative exploratory studies (neutrophil) [ Time Frame: 6 months ]
    neutrophil tumor infiltration will be associated to the rate of disease control patients at 6 months, PFS1, PFS2 and OS

  8. Biological correlative exploratory studies (cytokines) [ Time Frame: 6 months ]
    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

  9. Biological correlative exploratory studies (chemokines) [ Time Frame: 6 months ]
    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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.

  2. Histologically-proven NSCLC (squamous or non-squamous)
  3. Stage IV (M1, including M1a pleural involvement) disease (8th classification TNM, UICC 2015)
  4. ECOG PS < 1
  5. Weight loss< 10% in previous 3 months
  6. No prior systemic anticancer therapy (including EGFR or ALK inhibitors) given as primary therapy for advanced or metastatic disease.
  7. Age≥ 18 years, <75 years
  8. Life expectancy > 3 months
  9. Measurable tumor disease by CT or MRI per RECIST 1.1 criteria
  10. Available tumor samples for centralized PD-L1 immunohistochemistry analysis
  11. PD-L1 tumor content ≥ 1% and < 50% tumor cells as assessed locally by the investigator center
  12. 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)

  13. 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.

  14. Patient inclusion validated by a multidisciplinary meeting.

Exclusion Criteria:

  1. Small cell lung cancer or tumors with mixt histology including a SCLC component
  2. 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).
  3. Known ALK or ROS1 gene rearrangement as assessed by immunohistochemistry, FISH or NGS sequencing
  4. 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)
  5. Superior vena cava (SVC) syndrome persisting after SVC stenting
  6. 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
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. Active inflammatory intestinal disease (diverticulosis, Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea
  12. 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.
  13. HIV known infection
  14. Living attenuated vaccine received within the 30 previous days
  15. Previous treatment with anti-PD-1, anti-PD-L1 or Anti-CTLA4 antibody
  16. Previous treatment with chemotherapy
  17. 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
  18. Pre-existing lung interstitial disease as assessed by the diagnosis CT-scan.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03469960


Contacts
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Contact: Clinical Operations Manager 0156811046 ext 33 contact@ifct.fr

Locations
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France
Amiens - CHU Not yet recruiting
Amiens, France
Contact: Claire POULET, Pr       contact@ifct.fr   
Angers - CHU Not yet recruiting
Angers, France, 49000
Contact: Thierrry Urban, Pr         
Annecy - CH Not yet recruiting
Annecy, France, 74374
Contact: Dorine TEMPLEMENT, Dr         
Argenteuil -CH Not yet recruiting
Argenteuil, France, 95100
Contact: Laure BELMONT, Dr         
Contact       contact@ifct.fr   
Avignon - CH Recruiting
Avignon, France
Contact: Nicolas Cloarec, Dr         
Bordeaux - Polyclinique Nord Not yet recruiting
Bordeaux, France
Contact: Sigolène GALLAND-GIRODET, Dr       contact@ifct.fr   
Principal Investigator: Sigolène GALLAND GIRODET, Dr         
Boulogne - Ambroise Paré Recruiting
Boulogne-Billancourt, France
Contact: Etienne GIROUX-LEPRIEUR, MD         
Principal Investigator: Etienne GIROUX-LEPRIEUR, MD         
Caen - CHU Côte de Nacre Not yet recruiting
Caen, France, 14000
Contact: Jeannick MADELAINE, Dr         
Cahors - CH Not yet recruiting
Cahors, France, 46000
Contact: Patricia Barré, Dr         
CH de Pontoise Not yet recruiting
Cergy Pontoise, France
Contact: Cécile DURAND, Dr       contact@ifct.fr   
CH Chambery Not yet recruiting
Chambery, France
Contact: Anne BARANZELLI, Dr       contact@ifct.fr   
CH de Chauny Not yet recruiting
Chauny, France
Contact: Patrick DUMONT       contact@ifct.fr   
CH Recruiting
Cholet, France
Contact: Philippe MASSON         
Clamart - Hôpital Percy Recruiting
Clamart, France, 92140
Contact: Olivier BYLICKI, Dr       contact@ifct.fr   
Clermont Ferrand - CHU Not yet recruiting
Clermont Ferrand, France, 63000
Contact: Lise THIBONNIER, Dr         
Colmar - CH Not yet recruiting
Colmar, France, 68000
Contact: Lionel MOREAU, Dr         
Dijon - CAC Not yet recruiting
Dijon, France, 21000
Contact: Laure Favier, MD         
CHRU Grenoble Not yet recruiting
Grenoble, France
Contact: Anne-Claire TOFFART       contact@ifct.fr   
La Roche Sur Yon - CH Not yet recruiting
La Roche Sur Yon, France, 85925
Contact: Marie MARCQ, Dr         
Centre Hospitalier - Pneumologie Recruiting
Le Mans, France, 72000
Contact: Olivier Molinier, Dr         
CHRU de Lille Not yet recruiting
Lille, France
Contact: Alexis CORTOT, Pr       contact@ifct.fr   
CHU de Limoges Recruiting
Limoges, France
Contact: Thomas EGENOD, Dr       contact@ifct.fr   
CH Lyon Sud - Pneumologie Not yet recruiting
Lyon, France
Contact: Sébastien COURAUD       contact@ifct.fr   
Institut Paoli Calmette Recruiting
Marseille, France
Contact: Anne MADROSZYK, Dr       contact@ifct.fr   
Marseille - Hôpital Européen Not yet recruiting
Marseille, France
Contact: Jacques LE TREUT, Dr         
Mont de Marsan - CH Not yet recruiting
Mont de Marsan, France, 40000
Contact: Jérome Dauba, Dr       contact@ifct.fr   
Mulhouse - CH Not yet recruiting
Mulhouse, France, 68000
Contact: Didier DEBIEUVRE, Dr       contact@ifct.fr   
Nantes - Centre René Gauducheau Not yet recruiting
Nantes, France, 44805
Contact: Sandrine HIRET, Dr         
Centre Antoine Lacassagne Not yet recruiting
Nice, France
Contact: Josiane OTTO, MD       contact@ifct.fr   
CHU Nîmes Not yet recruiting
Nîmes, France
Contact: Sylvie VAN HULST, Dr       contact@ifct.fr   
Orléans - CH Not yet recruiting
Orléans, France, 45000
Contact: Adrien DIXMIER, Dr       contact@ifct.fr   
AP-HP Hopital Tenon - Pneumologie Not yet recruiting
Paris, France, 75020
Contact: Jacques Cadranel, Pr    +33.1.56.01.65.31    contact@ifct.fr   
Principal Investigator: Jacques Cadranel, pr         
AP-HP Hôpital Bichat Not yet recruiting
Paris, France
Contact: Gérard Zalcman, PhD       contact@ifct.fr   
GH Paris Saint-Joseph Not yet recruiting
Paris, France
Contact: Jean-Pierre TREDANIEL       contact@ifct.fr   
Hôpital Saint Louis APHP Not yet recruiting
Paris, France
Contact: Ludovic DOUCET, Dr       contact@ifct.fr   
Paris - Institut Curie Not yet recruiting
Paris, France
Contact: Sophie BEAUCAIRE-DANEL, Dr         
Rouen - CHU Not yet recruiting
Rouen, France, 76000
Contact: Luc Thiberville, Pr       contact@ifct.fr   
Saint Quentin - CH Not yet recruiting
Saint Quentin, France, 02100
Contact: Charles Dayen, Dr       contact@ifct.fr   
Centre René Huguenin Not yet recruiting
Saint-Cloud, France
Contact: Marie-Ange Massiani, Dr         
HIA Begin Not yet recruiting
Saint-Mandé, France
Contact: Carole HELISSEY, Dr       contact@ifct.fr   
ICL Lucien Neuwirth Not yet recruiting
Saint-Priest-en-Jarez, France
Contact: Pierre FOURNEL, Dr       contact@ifct.fr   
Suresnes - Hopital Foch Not yet recruiting
Suresnes, France, 92151
Contact: Sylvie Friard, Dr         
Toulon - CHI Not yet recruiting
Toulon, France, 83000
Contact: Clarisse Audigier-Valette, Dr       contact@ifct.fr   
CHU Toulouse Not yet recruiting
Toulouse, France
Contact: Julien MAZIERES, Pr       contact@ifct.fr   
CHRU de Tours Not yet recruiting
Tours, France
Contact: Eric PICHON, Dr       contact@ifct.fr   
Versailles - CH Not yet recruiting
Versailles, France, 78157
Contact: Cécile DUJON, Dr       contact@ifct.fr   
CH de Villefranche - Pneumologie Not yet recruiting
Villefranche, France
Contact: Luc ODIER       contact@ifct.fr   
Principal Investigator: Luc ODIER         
Sponsors and Collaborators
Intergroupe Francophone de Cancerologie Thoracique

Additional Information:
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Responsible Party: Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier: NCT03469960     History of Changes
Other Study ID Numbers: IFCT-1701
2017-002540-33 ( EudraCT Number )
First Posted: March 19, 2018    Key Record Dates
Last Update Posted: September 4, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Intergroupe Francophone de Cancerologie Thoracique:
IFCT
DICIPLE
NSCLC
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents