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
Overview
- Phase
- Phase 3
- Intervention
- Nivolumab + Ipilimumab
- Conditions
- Advanced Non Small Cell Lung Cancer
- Sponsor
- Rennes University Hospital
- Enrollment
- 217
- Locations
- 30
- Primary Endpoint
- Overall survival
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief 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.
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.
Investigators
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)
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),
Arms & Interventions
Nivolumab + Ipilimumab
Intervention: Nivolumab + Ipilimumab
Chemotherapy
carboplatin and pemetrexed or carboplatin and paclitaxel
Intervention: Chemotherapy
Outcomes
Primary Outcomes
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
Secondary Outcomes
- Survival rate(1 year)
- Quality of life score(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)
- PD-L1(2 years)
- Progression free survival(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 rate(2 years)
- Objective response rate(2 years)
- Tolerability rate(2 years)
- Geriatric evaluation(inclusion and 2 months)