| Eligibility |
Inclusion Criteria:
- Male or female, aged = 18 years old and = 75 years.
- ECOG Scale (Eastern Cooperative Oncology Group) of performance status of 0 or 1.
- Histologically or cytologically confirmed, non-resectable Stage IIIA-IIIB NSCLC
according to the 8th version of the International Association for the Study of Lung
Cancer Staging Manual in Thoracic Oncology.
- PET-CT (Positron Emission Tomography -Computed tomography) and brain computed
tomography or Magnetic resonance imaging (MRI) at baseline to confirm the absence of
distant disease.
- Mediastinal involvement could be considered without histological confirmation when no
margin can be distinguished in the lymph node mass.
- No prior treatment with anti-neoplastic drugs or thoracic radiotherapy for Stage
IIIA-IIIB NSCLC.
- Patients who have received prior neo-adjuvant, adjuvant chemotherapy with curative
intent for non-metastatic disease must have experienced a treatment-free interval of
at least 6 months from enrollment since the last chemotherapy.
- Presence of at least one measurable disease by CT-SCAN, as defined by RECIST v1.1.
- Adequate hematologic and organ function defined by the following laboratory results
obtained within 14 days prior to enrollment:
- Neutrophils = 1500 cells/µL without granulocyte colony-stimulating factor support.
- Lymphocyte count = 500/µL.
- Platelet count = 100,000/µL without transfusion.
- Haemoglobin = 10.0 g/dL. Patients may be transfused to meet this criterion.
- INR or aPTT = 1.5 × upper limit of normal (ULN). This applies only to patients who are
not receiving therapeutic anticoagulation; patients receiving therapeutic
anticoagulation should be on a stable dose.
- AST, ALT, and alkaline phosphatase = 2.5 × ULN, with the following exceptions:
- Serum bilirubin = 1.5 × ULN. Patients with known Gilbert disease who have serum
bilirubin level = 3 × ULN may be enrolled.
- Serum creatinine = 1.5 × ULN or creatinine clearance of =60ml/min (based on the
Cockcroft Gault formula).
- All patients are notified of the investigational nature of this study and signed a
written informed consent in accordance with institutional and national guidelines,
including the Declaration of Helsinki prior to any trial-related intervention.
- Adequate lung function: Forced Expiratory Volumen in 1 second (FEV1) >50% of normal
volume and Diffusion Capacity of the Lungs for Carbon Monoxide (DLCO) >40% of normal
value.
- No more than 35% of the total volume of the two lungs should receive more than 20 Gy
(V20) or no more than 7cm maximum diameter.
- For female patients of childbearing potential, agreement (by patient and/or partner)
to use a highly effective form(s) of contraception that results in a low failure rate
(< 1% per year) when used consistently and correctly, and to continue its use for 6
months after the last dose of trial treatment. Such methods include: combined
(oestrogen and progesterone containing) hormonal contraception, progestogen-only
hormonal contraception associated with inhibition of ovulation together with another
additional barrier method always containing a spermicide, intrauterine device (IUD):
intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised
partner (on the understanding that this is the only one partner during the whole study
duration), and sexual abstinence.
- For male patients with female partners of childbearing potential, agreement (by
patient and/or partner) to use a highly effective form(s) of contraception that
results in a low failure rate [< 1% per year] when used consistently and correctly,
and to continue its use for 6 months after the last dose of trial treatment. Male
patients should not donate sperm during this study and for at least 6 months after the
last dose of trial treatment.
- Oral contraception should always be combined with an additional contraceptive method
because of a potential interaction with the study drugs. The same rules are valid for
male patients involved in this clinical study if they have a partner of childbirth
potential. Male patients must always use a condom.
- Women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or
surgically sterile must have a negative serum pregnancy test result within 8 days
prior to initiation of study drug.
Exclusion Criteria:
- Patients with known sensitizing mutation or an amplification in the epidermal growth
factor receptor (EGFR) gene, ALK fusion oncogene.
- Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations.
- Weight loss >10% within the previous 3 months.
- Malignant pleural effusion or pericardial effusion: both will be considered as
suggestive of metastatic disease. Also excluded those with negative cytology but being
exudates.
- Patients with non-visible by thoracic X-Ray pleural effusion or too small to be safely
punctioned could be included.
- Malignancies other than NSCLC within 3 years prior to enrollment, with the exception
of those with a negligible risk of metastasis or death (e.g., expected 3-year OS >
90%) treated with expected curative outcome (such as adequately treated carcinoma in
situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer
treated with radiotherapy or surgically with curative intent, ductal carcinoma in situ
treated surgically with curative intent).
- Women who are pregnant, lactating, or intending to become pregnant during the study.
- Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster
ovary cells or any component of the Atezolizumab formulation.
- History of autoimmune disease.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan.
- Positive test for human immunodeficiency viruses (HIV). All patients will be tested
for HIV prior to inclusion into the study; patients who test positive for HIV will be
excluded from the clinical study.
- Patients with active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
- Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg)
are eligible only if they are negative for HBV DNA (vaccinated patients are excluded).
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is
negative for HCV RNA.
- Active tuberculosis.
- Symptomatic neuropathy (sensory) grade > 1 according to the NCI Common Toxicity
Criteria for Adverse Events v5.0
- Severe infections within 4 weeks prior to be included in the study, including but not
limited to hospitalization for complications of infection, bacteraemia, or severe
pneumonia.
- Received therapeutic oral or IV antibiotics within 2 weeks prior to be included in the
study.
- Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract
infection or to prevent chronic obstructive pulmonary disease exacerbation) are
eligible.
- Significant cardiovascular disease, such as New York Heart Association cardiac disease
(Class II or greater), myocardial infarction, or cerebrovascular accident within 3
months prior to inclusion, unstable arrhythmias, or unstable angina.
- Patients with known coronary artery disease, congestive heart failure not meeting the
above criteria, or left ventricular ejection fraction < 50% must be on a stable
medical regimen that is optimized in the opinion of the treating physician, in
consultation with a cardiologist if appropriate.
- Patients with a superior vena cava syndrome.
- Major surgical procedure other than for diagnosis within 28 days prior to inclusion or
anticipation of need for a major surgical procedure during the course of the study.
- Prior allogeneic bone marrow transplantation or solid organ transplant.
- Administration of a live, attenuated vaccine within 4 weeks before inclusion or
anticipation that such a live attenuated vaccine will be required during the study.
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical
laboratory finding giving reasonable suspicion of a disease or condition that
contraindicates the use of an investigational drug or that may affect the
interpretation of the results or renders the patient at high risk from treatment
complications.
- Patients with illnesses or conditions that interfere with their capacity to understand
follow and/or comply with study procedures.
- Treatment with any other investigational agent with therapeutic intent within 28 days
prior to initiation of study treatment.
- Treatment with systemic immunosuppressive medications (including but not limited to
corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to inclusion.
|
