EOpredict-Lung is a clinical study in subjects with histologically or cytologically confirmed, early stage or locally advanced non-small cell lung cancer (NSCLC) eligible for curative resection. This study will determine the feasibility of two cycles of preoperative immunotherapy with nivolumab or as combination nivolumab plus relatlimab.
- Conditions
- non-small cell lung cancer (NSCLC) of clinical stages IB, II and selected stage III AMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-002478-29-DE
- Lead Sponsor
- niversity Hospital Essen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
• Patients with histologically (core biopsy) or cytologically (e.g. bronchoscopy-guided biopsy) confirmed non-small cell lung cancer (NSCLC) eligible for anatomic resection, with the following specifications:
o Clinical stages I B, II and selected stage III A (T3 N1, T4 with satellite nodule in the same lung N0/N1, selected T1a-T2b N2 cases considered suitable for primary surgical approach by the multidisciplinary tumor board) according to UICC 8th edition
• Males and females, ages >= 18 years, inclusive
o Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [hCG]) within 24 hours prior to the start of study treatment.
o Women of childbearing potential (WOCBP) must agree to follow instructions for highly effective method(s) of contraception for the duration of treatment with study medication plus 5 months after the last dose of the study drug.
• ECOG = 1
• Exclusion of extensive mediastinal lymph node metastases (multilevel N2, N3) by PET/CT and/or invasive mediastinal lymph node staging by EBUS-TBNA and/or staging mediastinoscopy as indicated by current guidelines.
• Exclusion of distant metastases by standard of care imaging studies, which include but are not limited to PET/CT or PET/MRI, or CT or MRI of thorax, abdomen, pelvis, and bone scan. Asymptomatic brain metastases will be excluded by MRI or contrast-enhanced CT as indicated by current guidelines.
• Measurable target tumor prior to immunotherapy using standard imaging techniques.
• Sufficient pulmonary function to undergo curative lung cancer surgery, ppFEV1>30%, ppDLCO>30%, ppVO2max>=10 ml/min/kg (if CPET was mandated per local guidelines)
• Adequate hematological, hepatic and renal function parameters:
o Leukocytes = 2,000/mm³, platelets = 100,000/mm³, absolute neutrophil count (ANC) = 1,500/µL, hemoglobin = 9 g/dL (5.58 mmol/L),
o Anti-platelet therapy (such as but not limited to clopidogrel) should be discontinued pre-operatively according to local standards. If this therapy cannot be interrupted due to severe cardiovascular comorbidity, patient is ineligible for the trial
o Adequate coagulation function as defined by International Normalized Ratio (INR) = 1.5, and a partial thromboplastin time (PTT) = 5 seconds above the upper limit of normal (ULN) (unless receiving anticoagulation therapy). Patients receiving warfarin/phenprocoumon or direct oral anticoagulants are to be bridged according to local standards and have achieved stable coagulation profile prior to surgery.
o Serum creatinine = 1.5 x upper limit of normal
o Bilirubin = 1.5 x upper limit of normal, AST and ALT = 3.0 x upper limit of normal, alkaline phosphatase = 6 x upper limit of normal
• Sufficient cardiac left ventricular defined as LVEF = 50% documented either by echocardiography or MUGA (echocardiography preferred test, MUGA not used in German site) within 6 months before first administration of study drug
• Patient able and willing to provide written informed consent and to comply with the study protocol and with the planned surgical procedures
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30
•Active or history of autoimmune disease or immune deficiency, including, but not limited to [...]. Patients with the following conditions are not excluded from participation: *Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone * Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen * Skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic immunosuppressive treatment, in particular corticosteroids
•Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. [...]
•Subjects who have undergone organ transplant or allogeneic stem cell transplantation.
•ppFEV1<30%, ppDLCO<30%, ppVO2max <10 ml/min/kg (if CPET was mandated per local guidelines)
•Uncontrolled or significant cardiovascular disease including, but not limited to [...]
•History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, deep venous thrombosis, etc. )
•Cardiovascular disease-related requirement for daily supplemental oxygen
•History of two or more myocardial infarctions or two or more coronary revascularization procedures
•Subjects with history of myocarditis, regardless of etiology
•Troponin T (TnT) or I (TnI) >2× institutional ULN. [...]
•Patients with active neurological disease should be excluded.
•Active malignancy or a prior malignancy within the past 3 years. Patients with the following conditions are not excluded from participation: o Patients with completely resected basal cell carcinoma, cutaneous squamous cell carcinoma, cervical carcinoma insitu, breast carcinoma in-situ, non-invasive intestinal polyps, and patients with isolated elevation in prostate-specific antigen or low risk prostate cancer managed with active surveillance or
watchful waiting in the absence of radiographic evidence of metastatic prostate cancer.
•Known history of positive test for HIV-1 and HIV-2 or known AIDS. [...]
•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).
•Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
•Receipt of live attenuated vaccine within 30 days prior to the first dose of study medication
•Peripheral polyneuropathy NCI CTCAE Grade =2
•History of gastric perforation or fistulae in past 6 months
•Serious or non-healing wound, ulcer, or bone fracture within 28 days prior to enrollment.
•The patient has undergone major surgery within 28 days prior to enrollment except staging mediastinoscopy, diagnostic VATS or implantation of a venous port-system.
•Any other concurrent preoperative antineoplastic treatment including irradiation
•Pregnant women
•Breastfeeding women
•Insufficient cardiac left ventricular function defined as LVEF<50% by echocardiography (outside Germany: or MUGA scan) within 6 months before first a
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method