Durvalumab for Non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 1. Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIA, IIB, IIIA or IIIB (only T3N2) disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology)"}
• {"criterion_text":"- 10. 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."}
• {"criterion_text":"- 11. 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."}
• {"criterion_text":"- 12. 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."}
• {"criterion_text":"- 13. 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."}
• {"criterion_text":"- 14. Patients is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up"}
• {"criterion_text":"- 15. Presence of at least one measurable lesion by CT-SCAN, as defined by RECIST v1.1."}
• {"criterion_text":"- 16. Patients with a life expectancy ≥12 weeks"}
• {"criterion_text":"- 17. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol."}
• {"criterion_text":"- 2. PET scan and brain CT or MRI at baseline to confirm the absence of distant disease"}
• {"criterion_text":"- 3. ECOG (Performance status) 0-1"}
• {"criterion_text":"- 4. Adequate hematologic and organ function defined by laboratory results obtained within 14 days prior to enrolment - Neutrophils ≥ 1.5 x109/L without granulocyte colony-stimulating factor support. - Lymphocyte count ≥ 0.5 x109/L - Platelet count ≥ 100 x109/L without transfusion. Haemoglobin ≥ 10.0 g/dL. Patients may be transfused to meet this criterion. - Prothrombin 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 - 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 ≥50ml/min (based on the Cockcroft Gault formula)."}
• {"criterion_text":"- 5. All patients are notified of the investigational nature of this study and signed a written in-formed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention"}
• {"criterion_text":"- 6. 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"}
• {"criterion_text":"- 7. Patients aged ≥ 18 years at the time of study entry"}
• {"criterion_text":"- 8. Body weight > 30Kg (for durvalumab monotherapy)"}
• {"criterion_text":"- 9. PDL1 analyzed (value in %)"}

Exclusion criteria

• {"criterion_text":"- 1. Patients with known sensitizing mutation or an amplification in the epidermal growth factor receptor (EGFR) gene or any variety of alterations of ALK oncogene."}
• {"criterion_text":"- 10. Pleural or pericardial effusion, both will be considered indicative of metastatic disease unless proven otherwise. Patients with pleural effusion not visible on chest-X-ray or too small to perform diagnostic puncture safely may be included."}
• {"criterion_text":"- 11. Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction. Patients with a significant cardiac history, even if controlled, must have a LVEF > 50% within 12 weeks prior to randomization."}
• {"criterion_text":"- 12. 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."}
• {"criterion_text":"- 13. Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection. 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.\""}
• {"criterion_text":"- 14. Patients with history of allergy to study drug components/excipients or allergy to Rifaximin"}
• {"criterion_text":"- 15. Active tuberculosis"}
• {"criterion_text":"- 16. Severe infections within 4 weeks prior to be included in the study, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia."}
• {"criterion_text":"- 17. 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."}
• {"criterion_text":"- 18. 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."}
• {"criterion_text":"- 19. Patients with medical, mental, neurological or psychological condition which in the opinion of the investigator would not permit the patient to understand the patient information sheet or comply with study procedures."}
• {"criterion_text":"- 2. Known STK-11 ligand alterations, MDM2 amplifications or ROS1 translocations."}
• {"criterion_text":"- 20. Treatment with any other investigational agent with therapeutic intent within 28 days prior to initiation of study treatment."}
• {"criterion_text":"- 21. Patients with uncontrolled comorbidities that may affect the clinical trial compliance"}
• {"criterion_text":"- 22. Women who are pregnant or in the breastfeeding period or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy."}
• {"criterion_text":"- 23. Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study"}
• {"criterion_text":"- 24. Patients must be aware that they cannot be blood donors during the treatment of this clinical trial"}
• {"criterion_text":"- 25. Prior randomization or treatment in a previous durvalumab clinical study regardless of treatment arm assignment."}
• {"criterion_text":"- 26. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP."}
• {"criterion_text":"- 27. Concurrent enrolment in another clinical study, except if it is an observational (non-interventional) clinical study or during the follow-up period of this interventional study"}
• {"criterion_text":"- 3. Weight loss >10% within the previous 3 months"}
• {"criterion_text":"- 4. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable. Also, patients that receive previous treatment with chest radiotherapy, or previous surgery for lung cancer cannot be included."}
• {"criterion_text":"- 5. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy"}
• {"criterion_text":"- 6. History of active primary immunodeficiency"}
• {"criterion_text":"- 7. History of another primary malignancy except for: a. Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of IP and of low potential risk for recurrence b. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease c. Adequately treated carcinoma in situ without evidence of disease"}
• {"criterion_text":"- 8. Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: a. Patients with vitiligo or alopecia b. Patients with hypothyroidism stable on hormone replacement c. Any chronic skin condition that does not require systemic therapy d. Patients without active disease in the last 5 years may be included but only after consultation with the study physician e. Patients with celiac disease controlled by diet alone"}
• {"criterion_text":"- 9. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease"}

Primary endpoints

• {"endpoint_text":"- The primary objective is to evaluate the pathological Complete Response (pCR) rate in the intention to treat population (ITT population) Pathological Complete Response (pCR) defined as the absence of residual tumor in lung and lymph nodes after surgery.","definition_or_measurement_approach":"Pathological Complete Response (pCR) defined as the absence of residual tumor in lung and lymph nodes after surgery; pCR rate evaluated in the intention-to-treat (ITT) population."}

Secondary endpoints

• {"endpoint_text":"- 1. Progression free survival (PFS) rate at 12 and 24 months","definition_or_measurement_approach":"PFS rate measured at 12 and 24 months (time-to-event analysis as progression-free survival)."}
• {"endpoint_text":"- 2. Overall survival (OS) rate at 12 and 24 months of treatment","definition_or_measurement_approach":"Overall survival rate measured at 12 and 24 months."}
• {"endpoint_text":"- 3. Resectability rate (%)","definition_or_measurement_approach":"Proportion of patients deemed resectable (percentage)."}
• {"endpoint_text":"- 4. Proportion of R0 resections (%)","definition_or_measurement_approach":"Proportion of complete (R0) resections as percentage."}
• {"endpoint_text":"- 5. Safety and tolerability of the treatment: Adverse events graded according to CTCAEv 5.0","definition_or_measurement_approach":"Adverse events collected and graded per CTCAE v5.0 to assess safety and tolerability."}

Spain

Earliest CTIS Part Ii Submission Date

01-09-2025

Latest Decision Or Authorization Date

08-09-2025

Processing Time Days

7

Number Of Sites

19

Number Of Participants

68

Primary sponsor

Full Name

Fundacion GECP

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain