Non-small cell lung cancer with brain metastasis MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Fundación GECP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. COHORT A - Patients with histologically or cytologically confirmed stage IV NSCLC who did not receive any prior systemic therapy for advanced disease and have synchronous untreated brain metastases which does not cause neurologic symptoms and does not require systemic corticosteroid treatment within 10 days before initiating study treatment (controlled seizures with antiepileptic drugs should be allowed). 2. COHORT B: -Patients with histologically or cytolotically confirmed stage IV NSCLC who did not receive any prior systemic therapy for advanced disease and have synchronous brain metastasis causing neurologic signs and symptoms controlled with medium-low doses of corticosteroids (= 25mg/d of prednisone or = 4mg/d of dexamethasone) but have good performance status (ECOG PS0-1). -At least one untreated brain lesion in patients who already received focal radiotherapy (stereotactic focal radiotherapy) of prior brain lesions are eligible if novel brain lesions appear which are measur-able and not suitable for focal radiotherapy.3. Patients with early or locally advanced NSCLC who have recurred after 6 months of completing adjuvant or neoadjuvant chemotherapy and have brain metastases are also eligible 3. ECOG performance status 0-1 4. Patients aged = 18 years 5. Systemic measurable disease by computed tomography (CT) per response evaluation criteria in solid tumors version (RECIST) 1.1 criteria and brain measurable disease by magnetic resonance im-aging (MRI) per RANO-BM criteria 6.Availability of a formalin-fixed paraffin-embedded block containing tumor tissue or 10 unstained slides. Archival tumor tissue can be sent if it was obtained less than 12 months ago. 7.Correct hematological, hepatic and renal function i. Neutrophils = 1500×109/L ii. Platelets = 100 ×109/L iii. Hemoglobin = 9.0 g/dL iv. Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 45 mL/min (if using the Cockcroft-Gault formula below): a. Female CrCl = (140 - age in years) x weight in kg x 0.85/ 72 x serum creatinine in mg/dL b. Male CrCl = (140 - age in years) x weight in kg x 1.00/ 72 x serum creatinine in mg/dL v. AST/ALT = 3 x ULN. Patients with documented liver metastases: AST and/or ALT = 5 × ULN vi. Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 71
Exclusion criteria
Exclusion criteria: 1. Patients with a history of other malignant diseases within the past 3 years, with the exception of the following: o properly treated non-melanotic skin cancer o cancer in situ treated with curative intent o nonmuscularis propia invasive carcinoma of the bladder o or other malignancies treated with curative intent and without signs of disease for a period of > 3 years after the end of the treatment and which, in the opinion of the physician in charge of their treatment, do not present a substantial risk of relapse of the previous malignant disease. 2. Patients harboring epidermal growth factor receptor (EGFR) mutations or anaplastic lym-phoma kinase (ALK) and ROS Proto-Oncogene 1 (ROS1) rearrangements sensitive to available targeted inhibitor therapy 3. Patients with a combination of small cell lung cancer and non-small cell lung cancer, a carcinoid lung tumor or large cell neuroendocrine carcinoma 4. Patients that received live attenuated vaccines within 30 days prior to randomization 5. Leptomeningeal carcinomatosis or metastases in the brain stem, midbrain, pons, medulla or causing obstructive hydrocephalus 6. Single exclusive brain metastasis amenable to surgical treatment or radiosurgery 7. Prior surgical resection of brain or spinal lesions in the prior 28 days 8. Patients who have received prior neoadjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease less than 6 months before enrollment since the last chemotherapy, radiotherapy, or chemoradiotherapy 9. History of a primary immunodeficiency, history of organ allogeneic transplantation, use of immunosuppressive drugs within 28 days before randomization or previous history of tox-icity of severe immune mechanism (grade 3 or 4) with other immunological treatments 10. Patients with an active, known or suspected autoimmune disease. Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to be enrolled 11. Patients with active or uncontrolled infections or with serious medical conditions or disor-ders that may not allow patient management as established in the protocol 12. History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of radiation pneumonitis put of the radiation field on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted. 13. Significant comorbidities that preclude the administration of chemotherapy according to the investigator’s criteria 14. Any positive test result for hepatitis B virus or hepatitis C virus indicating presence of virus, e.g. Hepatitis B surface antigen (HBsAg, Australia antigen) positive, or Hepatitis C antibody (anti-HCV) positive (except if HCV-RNA negative) 15. Previous treatment with immune checkpoint inhibitors 16. Patients who have suffered untreated and / or uncontrolled cardiovascular disorders and / or who have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction in the previous year or ventricular cardiac arrhythmias that require med-ication, history of atrioventricular conduction of second or third degree) 17. Pregnant or breastfeeding women 18. History of allergy o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this trial is to determine the rate of intracranial clinical benefit, defined as the percentage of patients who had lack of radiological or clinical progression for at least 6 months according to RANO-BM assessment criteria;Secondary Objective: -To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). -To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of the investigator assessed bicompartimental PFS defined as systemic PFS (excluding CNS) as per RECIST version 1.1 and PFS in the CNS as per RANO-BM criteria -To evaluate the safety of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases. - Overall survival (OS) at 12, 18 and 24 defined as the time from enrollment to death from any cause at this landmark timepoints -To determine the quality of life (QoL);Primary end point(s): The primary objective of this trial is to determine the rate of intracranial clinical benefit, defined as the percentage of patients who had lack of radiological or clinical progression for at least 6 months according to RANO-BM assessment criteria.;Timepoint(s) of evaluation of this end point: at the end of the follow up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). -To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases in terms of the investigator assessed bicompartimental PFS defined as systemic PFS (excluding CNS) as per RECIST version 1.1 and PFS in the CNS as per RANO-BM criteria -To evaluate the safety of Nivolumab + Ipilimumab + 2 cycles of chemotherapy in patients with NSCLC and synchronous brain metastases. - Overall survival (OS) at 12, 18 and 24 defined as the time from enrollment to death from any cause at this landmark timepoints -To determine the quality of life (QoL);Timepoint(s) of evaluation of this end point: -To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of CT in patients with NSCLC and synchronous brain metastases in terms of objective response rate (ORR), duration of response, progression-free survival (PFS) and overall survival (OS)at the end of follow up. -To evaluate the efficacy of Nivolumab + Ipilimumab + 2 cycles of CT in patients with NSCLC and synchronous brain metastases in terms of the investigator assessed bicompartimental PFS defined as systemic PFS (excluding CNS) as per RECIST version 1.1 and PFS in the CNS as per RANO-BM criteria at the end of follow up -To evaluate the safety of Nivolumab + Ipilimumab + 2 cycles of CT in patients with NSCLC and synchronous brain metastases at the end of follow up - OS at 12, 18 and 24 month -QoL at the end of follow up | — |
Countries
Spain
Contacts
Public ContactEva Pereira
Fundación GECP
Outcome results
None listed