Atezolizumab Plus Induction Chemotherapy Plus CT-radiotherapy. (APOLO)

• Status: Recruiting
• Trial end date: 2027-11-15
• Target enrollment: 0
• Participant gender: All

Summary

Open-label, non-randomized, phase II multi-centre controlled clinical trial.

51 non-resectable stage IIIA-IIIB non-small cell lung cancer patients will be enrolled in this trial to evaluate the efficacy of the treatment (Atezolizumab + Induction chemotherapy (CT) + CT-Radiotherapy) in terms of the Progression Free Survival at 12 months

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fundación GECP
• Treatments: Atezolizumab; Carboplatin

Criteria

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.