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

NCT03351361

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Randomized Phase III Study Testing Nivolumab and Ipilimumab Versus a Carboplatin Based Doublet in First Line Treatment of PS 2 or Elderly Patients With Advanced Non-small Cell Lung Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: 2017-002842-60
  • SECONDARY ID: 35RC16_9734
  • SECONDARY ID: 08-2015
  • SECONDARY ID: CA209-449
  • NCT ID: NCT03351361

Conditions

  • Advanced Non Small Cell Lung Cancer

Interventions

DrugSynonymsArms
Nivolumab + IpilimumabNivolumab + Ipilimumab
ChemotherapyChemotherapy

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Nivolumab + IpilimumabExperimental
  • Nivolumab + Ipilimumab
ChemotherapyActive Comparatorcarboplatin and pemetrexed or carboplatin and paclitaxel
  • Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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.

        Exclusion Criteria:

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Survival rate
Time Frame:1 year
Safety Issue:
Description:
Measure:Objective response rate
Time Frame:2 years
Safety Issue:
Description:according to RECIST 1.1
Measure:Progression free survival
Time Frame: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
Safety Issue:
Description:
Measure:Safety
Time Frame:2 years
Safety Issue:
Description:according to CTCAE version 4.0
Measure:Tolerability
Time Frame:2 years
Safety Issue:
Description:according to CTCAE version 4.0
Measure:Quality of life
Time Frame: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
Safety Issue:
Description:according to EQ-5D questionnaire
Measure:Quality of life
Time Frame: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
Safety Issue:
Description:according to EORTC QLQ-ELD14 questionnaire
Measure:PD-L1
Time Frame:2 years
Safety Issue:
Description:testing by immunochemistry
Measure:Geriatric evaluation
Time Frame:inclusion and 2 months
Safety Issue:
Description:according to geriatric mini data set

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Rennes University Hospital

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