patients with advanced NSCLC MedDRA version: 20.0 Level: LLT Classification code 10001160 Term: Adenocarcinoma lung System Organ Class: 100000004864
Conditions
Interventions
Trade Name: CARBOPLATINO SANDOZ GMBH - 10MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO IN VETRO DA 60ML
Product Name: CARBOPLATINO
Product Code: [CARBOPLATINO]
Pharmaceutical Form: Conc
Sponsors
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female ³ 70 years of age. Histological documentation of primary squamous or non squamous non-small cell lung carcinoma. Stage IV or IIIC disease with supraclavear metastatic nodes (according to TNM 8th edition). PD-L1 expression in tumor cells (TC) = 25%* or unknown due to lack of tumor specimen (no more than 25% of the overall sample size will be allowed) Clinical or radiologic evidence of disease (at least one measurable or non measurable lesion). ECOG performance status 0 to 1. Life expectancy > 3 months. Adequate renal and hepatic function, defined as: Total serum bilirubin = 1.5 institutional ULN. AST and/or ALT = 2.5 x ULN for the institution (or = 5 x ULN if liver metastases are present) Serum creatinine = 1.5 x ULN for the institution (or calculated creatinine clearance = 40 mL/min/1.73 m2). Adequate bone marrow function, defined as: Haemoglobin ³ 9.0 g/dL Absolute Neutrophils count (ANC) ³ 1.5 x 109/L (> 1500 per mm3) Platelet count ³ 100 x 109/L(>100,000 per mm3). Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. *Note: patients with PD-L1 TC = 50% should receive standard first-line pembrolizumab, if available in clinical practice. Therefore, their enrollment in the MILES-5 study is not encouraged. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240
Exclusion criteria
Exclusion criteria: Cancer related 1. Activating epidermal growth factor receptor mutation (exon19 deletion or exon 21 L858R mutation or other activating/sensitizing mutations). 2. ALK or ROS1 positive (immunohistochemistry or FISH) 3. Mixed small-cell lung cancer and NSCLC histology. Prior, current or planned treatment related 4. Prior chemotherapy or any other medical treatment for advanced NSCLC (previous neoadjuvant or adjuvant chemotherapy is allowed if > 6 months previously). 5. Prior exposure to immunomodulatory therapy, including, but not limited to, other anti-programmed cell death1 (PD-1), anti-programmed cell death ligand 1 (PD-L1), or anti PD-L2 antibodies. 6. Current or prior use of immunosuppressive medication within 14 days before the first dose of study treatment ( corticosteroids at physiological doses not exceeding 10 mg/day of prednisone or an equivalent corticosteroid are allowed). 7. Any concurrent investigational product or other anticancer treatment. Prior or concomitant conditions or procedures related 8. Active or prior documented autoimmune disease within the past 2 years (subjects with vitiligo, Grave’s disease, or psoriasis not requiring systemic treatment within the past 2 years, are not excluded). 9. Active or prior documented inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis) 10. History of allogeneic organ transplant 11. History of active primary immunodeficiency. 12. Active infection, including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. 13. Receipt of live attenuated vaccine within 30 days prior to the first dose of study drugs. 14. Patients with previous malignancies in the last 5 years (except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer or surgically resected prostate cancer with normal PSA) 15. Brain metastases or spinal cord compression, unless asymptomatic, previously treated, and stable off steroids and anti-convulsants for at least one month prior to study entry. 16. Leptomeningeal carcinomatosis 17. Clinically significant cardiovascular disease, including: a. Myocardial infarction or unstable angina pectoris within grade 3 (i.e. symptomatic and interfering with activities of daily living requiring repair or revision) f. Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia’s Correction. 18. Known hypersensitivity to any of the study drugs or excipients. 19. Evidence of any other concomitant illness, physical examination or laboratory findings (including but not limited to interstitial lung disease, active peptic ulcer disease or gast
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the preliminary efficacy (in terms of 12-month overall survival) of an experimental strategy (first-line treatment with durvalumab followed at progression by standard chemotherapy), compared to standard chemotherapy followed at progression by durvalumab, in the elderly population with PDL1 =25% or unknown. To assess the safety (in terms of death rate within 4 months from randomization) of durvalumab compared to standard chemotherapy.;Secondary Objective: To compare the two arms in terms of: •first progression-free survival (PFS) •quality of life (EORTC C30 + LC13) •toxicity profile (CTCAE 5.0 version and PRO-CTCAE) •objective response rate (RECIST v.1.1. and iRECIST) •second progression-free survival (PFS2) To test whether an interaction exists between treatments effect and PD-L1 status (=25% vs unknownpositive vs negative). To explore the predictive value of TMB (tumor mutation burden) measured in baseline blood sample. To explore the prognostic and predictive value of geriatric evaluation outcomes assessed through ADL, IADL, G8, CIRS and gait speed test. To explore the prognostic or predicitive value of the number and type of tumor lesions. To explore other possible predictive or prognostic factors (clinical, or measurable in the tumor or measurable in the blood) and their interaction with treatment arms.;Primary end point(s): 1) 12-month overall survival 2) 4-month mortality rate;Timepoint(s) of evaluation of this end point: 1) 12 month 2) 4 month | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): second progression-free survival (PFS2); first progression-free survival (PFS) ; quality of life (EORTC C30 + LC13); toxicity profile (CTCAE 5.0 version and PRO-CTCAE); objective response rate (RECIST v.1.1. and iRECIST);Timepoint(s) of evaluation of this end point: Tumor assessments with CT scan will be performed at baseline, during weeks 8-9, during weeks 16-17, at 6, 9 and 12 months, and every 4 months thereafter; Tumor assessments with CT scan will be performed at baseline, during weeks 8-9, during weeks 16-17, at 6, 9 and 12 months, and every 4 months thereafter; Quality of life in this trial will be assessed at baseline (before randomization), every 4 weeks for the first 16 weeks, every 3 months until 12 months from randomization and every 4 months thereafter, concomitantly with follow-up visits for restaging, until disease-progression. ; every 3/4 weeks; Tumor assessments with CT scan will be performed at baseline, during weeks 8-9, during weeks 16-17, at 6, 9 and 12 months, and every 4 months thereafter | — |
Countries
Italy
Contacts
Public ContactUnità Sperimentazioni Cliniche
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Outcome results
None listed