Exploratory study evaluating the potential of immune signature profiling for predicting response in patients with resectable Stage II, IIIA and select IIIB (T3N2 only) non-squamous Non-Small Cell Lung Cancer (NSCLC) to neoadjuvant ATEZOLIZUMAB plus Carboplatin/Nab Paclitaxe
- Conditions
- resectable Stage II, IIIA and select IIIB non-squamous Non-Small Cell Lung CancerMedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000388-21-DE
- Lead Sponsor
- Ruprecht-Karls University Heidelberg, Medical Faculty, repr. by HD University Hospital and its Commercial Managing Dir.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 20
?Willing and able to sign a written informed consent form (ICF
?Informed consent, patients age = 18-year-old including, signed and dated
?Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
?Histologically confirmed NSCLC of non-squamous histology, cStage II, IIIA or select IIIB (T3N2 only); for T-status = T3 allowed; for N2 patients only IIIa1-3 Robinson classification allowed
?Deemed surgically resectable with curative intent by an attending thoracic surgeon after adequate staging including PET-CT
?Adequate lung and cardiac function for intended lung resection according to German S3 regulation
?Radiologically measurable disease as defined by response evaluation criteria in solid tumors RECIST v1.1
?Sufficient availability of the tissue sample from primary tumor before start of neoadjuvant treatment
?Females of child-bearing potential must agree to use, and be able to comply with, effective contraception (?Females must have a negative serum pregnancy test (ß -hCG) result at screening and agree to ongoing pregnancy testing during the course of the study, and after the end of study therapy.
?Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following treatment discontinuation, even if he has undergone a successful vasectomy.
?adequate renal, hepatic, and bone marrow function as defined below
?Absolute neutrophil count (ANC) > 1500/µl
?Platelet count = 100000/µl
?Hemoglobin = 9 g/dl (can be post-transfusion)
?International normalized ratio (INR) = 1.4 in patients not receiving anticoagulation; for patients receiving respective anticoagulation an INR =3.0 allowed
?Activated partial thromboplastin time (aPTT) = 1.5 times upper limit of normal (ULN) in patients not receiving anticoagulation; for patients receiving respective anticoagulation a PTT =2.5 ULN allowed
?Bilirubin < 1.5 times ULN (for patients with known Gilbert disease Bilirubin = 3 times ULN allowed)
?ALT and AST < 2.5 times ULN
?Creatinine = 1.5 ULN or calculated creatinine clearance > 60 ml/min for subjects with creatinine levels > 1.5 ULN; for patients meeting the criterion of creatinine = 1.5 ULN also a calculated creatinine clearance of > 30 ml/min is mandatory
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 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5
1.Illness or condition that may interfere with a patient’s capacity to understand, follow, and/or comply with study procedures
2.Treatment in any other clinical trial within 30 days before screening.
3.NSCLC Stage cT4
4.NSCLC stage cN3 or cN2 IIIA4 (bulky or fixed multi-station N2 disease) according to Robinson classification
5.NSCLC of squamous cell histology
6.Any prior therapy for lung cancer (including systemic therapy, radiotherapy or major surgery)
7.Malignancies other than NSCLC within 5 years prior to study inclusion with the exception of malignancies with a negligible risk of metastasis or death (5-year OS > 90%) like localized prostate cancer, ductal carcinoma in situ, adequately treated carcinoma in situ of the cervix, Stage I uterine cancer or non-melanoma skin carcinoma
8.History of allogeneic tissue / solid organ transplant or allogeneic stem cell transplantation
9.Patients with active hepatitis B or C infections or a history of HIV infection.
10.Pregnant or lactating women
11.Active autoimmune disease or history of severe autoimmune disease or immunodeficiency or a syndrome that requires systemic steroids or immunosuppressive agents
12.The following exceptions are granted:
opatients with vitiligo, eczema, lichen simplex or resolved childhood asthma/atopy
osubjects requiring intermittent use of bronchodilators or local steroid injections
opatients with hypothyroidism stable on hormone replacement
13.Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, and anti-tumor necrosis factor (anti-TNF) agents) within 2 weeks prior to Cycle 1, Day 1 (except low-dose steroids for adrenal failure or emesis prophylaxis)
14.History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia, drug-induced pneumonitis, or evidence of active pneumonitis on screening chest Computed Tomography (CT) scan.
15.Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody
16.Live vaccine within 30 days prior to first dose of trial treatment
17.Cerebrovascular accident within the past 6 months
18.Severe infection or significant traumatic injury within the past 4 weeks
19.Clinically significant history of cardiovascular disease, including any of the following:
oMyocardial infarction or unstable angina within the past 6 months
oNew York Heart Association class II, III-IV congestive heart failure
oPoorly controlled cardiac arrhythmia despite medication, except rate-controlled atrial fibrillation
20.Known allergy or hypersensitivity to any component of the chemotherapy regimen
21.Patients who have been incarcerated or involuntarily institutionalized by court order or by the authorities, as well as patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial
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