NIVOLUMAB for Non-small cell lung cancer | Pancoast tumour

Inclusion criteria

• {"criterion_text":"- 1. Previously untreated patients with histologically or cytologicallydocumented NSCLC diagnosed with Pancoast tumor according to 8th edition of the TNM (stages IIB, IIIA and T3N2 (IIIB) patients)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 11. Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before enrollment."}
• {"criterion_text":"- 12. All sexually active men and women of childbearing potential must use an effective contracep-tive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs"}
• {"criterion_text":"- 13. Patient capable of proper therapeutic compliance and accessible for correct follow-up."}
• {"criterion_text":"- 2. PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before enrollment) to rule out the presence of distant disease. Also, a brain CT-SCAN or brain MRI will be done at baseline"}
• {"criterion_text":"- 3. Positive mediastinal lymph nodes by PET-CT must be confirmed histologically. Mediastinal involvement may be considered without the need for histological confirmation when there is a mass of lymph nodes in which the margins cannot be distinguished"}
• {"criterion_text":"- 4. Measurable or evaluable disease (according to RECIST 1.1 criteria)"}
• {"criterion_text":"- 5. ECOG (Performance status) 0-2"}
• {"criterion_text":"- 6. Patients with a life expectancy of at least more than 12 weeks"}
• {"criterion_text":"- 7. Patients aged > 18 years and ≤ 75 years"}
• {"criterion_text":"- 8. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to enrollment i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 ×109/L iii. Hemoglobin > 10.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula below): a. Female CrCl = (140 - age in years) x weight in kg x 0.85/ 72 x serum creatinine in mg/dL b. Male CrCl = (140 - age in years) x weight in kg x 1.00/ 72 x serum creatinine in mg/dL v. AST/ALT ≤ 2.5 x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or >40% predicted value viii. INR/APTT within normal limits"}
• {"criterion_text":"- 9. Correct lung function without bronchodilators, defined by forced expiratory volume in 1 second (FEV1) >40% of the predicted normal volume, and a pulmonary diffusing capacity for carbon monoxide (DLCO) >40% of the predicted normal value"}

Exclusion criteria

• {"criterion_text":"- 1. Patients that receive previous treatment with antineoplastic drugs, chest radiotherapy, or previous surgery for lung cancer or for another reason"}
• {"criterion_text":"- 10. Patients with uncontrolled comorbidities that may affect the clinical trial compliance"}
• {"criterion_text":"- 11. Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 5 years prior to study entry AND no additional therapy is required during the study period."}
• {"criterion_text":"- 12. Any medical, mental, neurological or psychological condition which in the opinion of the in-vestigator would not permit the patient to complete the study or understand the patient information sheet."}
• {"criterion_text":"- 13. Patients in any psychological, familiar, sociological or geographical situation that may hinder compliance with the study protocol and/or the follow up"}
• {"criterion_text":"- 14. Patients who have had prior treatment with an anti-PD-1, anti-PDL1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways"}
• {"criterion_text":"- 15. 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"}
• {"criterion_text":"- 16. Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)"}
• {"criterion_text":"- 17. Patients with know hypersensitivity to drugs with a structure similar to the study drug and/or history of allergy to study drug components excipients"}
• {"criterion_text":"- 18. Women who are pregnant or in the period of breastfeeding"}
• {"criterion_text":"- 19. Sexually active men and women of childbearing potential who are not willing to use an ef-fective contraceptive method during the study"}
• {"criterion_text":"- 2. Pleural or pericardial effusion: Both will be considered indicative of metastatic disease unless proven otherwise. Those that, even being cytologically negative for malignancy, are exudates, will also be excluded. Patients with pleural effusion not visible on chest X-ray or too small to perform diagnostic puncture safely may be included."}
• {"criterion_text":"- 3. Patients with a weight loss >10% in the 3 months prior to the study entry"}
• {"criterion_text":"- 4. All patients carrying activating mutations in the TK domain of EGFR or any variety of altera-tions in the ALK gene or ROS1 mutations."}
• {"criterion_text":"- 5. Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hor-mone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included."}
• {"criterion_text":"- 6. Patients with symptomatic neuropathy > grade 1 according to the CTCAE v5.0 and that were not related to the tumor"}
• {"criterion_text":"- 7. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease."}
• {"criterion_text":"- 8. Patients with a history of interstitial lung disease cannot be included if they have sympthomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team.case of doubt please contact trial team."}
• {"criterion_text":"- 9. Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy"}

Primary endpoints

• {"endpoint_text":"- The primary objective is to estimate progression-free survival (PFS) at 24 months from enrollment. The PFS is defined as the time from enrollment to relapse, progression or death, whichever occurred first.","definition_or_measurement_approach":"Estimate progression-free survival (PFS) at 24 months from enrollment. PFS defined as time from enrollment to relapse, progression or death; measured by clinical and radiological assessment according to study schedule."}

Secondary endpoints

• {"endpoint_text":"- 1. Overall survival rate (OS) at 24 months: Overall survival is defined as the time between the date of enrollment and the date of death. OS will be censored on the last date a participant was known to be alive","definition_or_measurement_approach":"Overall survival at 24 months; OS defined as time from enrollment to death; censoring at last known alive date."}
• {"endpoint_text":"- 2. Complete resection (R0) after induction treatment with chemotherapy plus nivolumab","definition_or_measurement_approach":"Binary surgical outcome after induction therapy: proportion achieving complete (R0) resection."}
• {"endpoint_text":"- 3. Objective treatment response rate (ORR), Disease control rate (DCR) and Duration of response (DOR). Systemic ORR, defined as a complete or partial response as determined by the investigator according to RECIST v1.1.","definition_or_measurement_approach":"ORR and DCR per RECIST v1.1 as assessed by investigator; DOR measured from first documented response to progression or death."}
• {"endpoint_text":"- 4. Pathological response and percentage of Residual tumor viable (RTV%) in the primary tumor: pathological complete response (pCR) defined as the absence of residual tumor, Major pathological response rate (MPR), defined as number of randomized participants with <10% residual tumor","definition_or_measurement_approach":"Pathological response assessed on surgical specimen: pCR = absence of residual tumor; MPR = <10% residual viable tumor; RTV% reported."}
• {"endpoint_text":"- 5. Treatment safety and tolerability","definition_or_measurement_approach":"Safety assessed by collection of adverse events and laboratory abnormalities; tolerability by treatment discontinuations and dose modifications."}
• {"endpoint_text":"- 6.Study of the prognostic value of basal ctDNA (association of basal levels with PFS and OS) and to assess the minimal residual disease (MRD) in plasma samples","definition_or_measurement_approach":"Baseline circulating tumour DNA (ctDNA) levels correlated with PFS and OS; MRD assessment in plasma samples using specified molecular assays."}
• {"endpoint_text":"- 7. To assess minimal residual disease (MRD) in the baseline tumor sample before treatment","definition_or_measurement_approach":"Assessment of MRD on baseline tumour sample (tissue) prior to treatment using molecular methods; association with outcomes."}

Spain

Earliest CTIS Part Ii Submission Date

11-03-2024

Latest Decision Or Authorization Date

06-04-2026

Processing Time Days

756

Number Of Sites

29

Number Of Participants

22

Primary sponsor

Full Name

Fundacion GECP

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain