Study of Atezolizumab plus chemotherapy plus chemo-radiotherapy and Atezolizumab maintenance therapy in non-resectable non-small cell lung cancer patients

Phase 1

• Conditions: on small cell lung cancer; MedDRA 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: EUCTR2020-004459-33-ES
• Lead Sponsor: Fundación GECP

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-09-01
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

1.Male or female, aged = 18 years old and = 75 years
2.ECOG performance status of 0 or 1.
3.Histologically or cytologically confirmed, non-resectable Stage IIIA-IIIB non-squamous NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology
4.PET-CT and brain CT or MRI at baseline to confirm the absence of distant disease
5.Mediastinal involvement could be considered without histological confirmation when no margin can be distinguished in the lymph node mass.
6.No prior treatment with anti-neoplasic drugs or thoracic radiotherapy for Stage IIIA-IIIB non-squamous NSCLC.
7.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.
8.Presence of at least one measurable disease by CT-SCAN, as defined by RECIST v1.1.
9.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).
10.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.
11.Adequate lung function: Forced Espiratoy Volumen in 1 second (FEV1) >50% of normal volume and Difusion Capacity of the Lungs for Carbon Monoxide (DLCO) >40% of normal value
12.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
13.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 5 months after the last dose of Atezolizumab and/or 6 months after the last dose of Bevacizumab, whichever is later. Such methods include: combined (oestrogen and progestogen 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, vasectomized partner (on the understanding that this is the only one partner during the whole study duration), and sexual abstinence.
14.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

Exclusion Criteria

1.Patients with a sensitizing mutation or an amplification in the epidermal growth factor receptor (EGFR) gene, ALK fusion oncogene
2.Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations.
3.Weight loss >10% within the previous 3 months.
4.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.
5.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).
6.Women who are pregnant, lactating, or intending to become pregnant during the study.
7.Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the Atezolizumab formulation.
8.History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
9.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.
10.Positive test for 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.
11.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.
12.Active tuberculosis.
13.Symptomatic neuropathy (sensory) grade > 1 according to the NCI Common Toxicity Criteria for Adverse Events v5.0
14.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.
15.Received therapeutic oral or IV antibiotics within 2 weeks prior to be included in the study.
16.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 appropri

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified