Patients with high-risk, metastatic (Stage IV) squamous or non-squamous NSCLC. MedDRA version: 21.1 Level: LLT Classification code 10064049 Term: Lung adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Interventions
Product Name: Durvalumab
Product Code: Durvalumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Durvalumab
CAS Number: 1428935-60-7
Current Sponsor code: MEDI4736
Concentration unit:
Sponsors
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Si rimanda alle pag. 15/18 del protocollo Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 4.2.1 Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for = 3 years. 4.2.2 Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn’s disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion: • Patients with alopecia. • Patients with Grave’s disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years). • Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement. 4.2.3 History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade = 3 infusion reaction. 4.2.4 Live attenuated vaccination administered within 30 days prior to randomization. 4.2.5 History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients who have received other treatment or other antibodies must not have had intolerable toxicity or required steroids to manage toxicity. 4.2.6 Mean QT interval corrected for heart rate using Fridericia’s formula (QTcF) = 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome. 4.2.7 Patients who have untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if now controlled, should have a LVEF = 45%. (Note: patients with uncomplicated controlled hypertension do not require LVEF measurement in the absence of other significant cardiac history) 4.2.8 Concurrent treatment with other investigational drugs or anti-cancer therapy 4.2.9 Patients with untreated brain or meningeal metastases are not eligible. Patients with treated CNS disease who have radiologic AND clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization). 4.2.10 Pregnant or Lactating Women: Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to randomization. If urine test is positive, pregnancy testing may then include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy. Men an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the overall survival (OS) of patients receiving durvalumab, tremelimumab plus platinum-based chemotherapy to that of patients receiving durvalumab and tremelimumab alone.;Secondary Objective: ¿ To compare progression free survival (PFS; RECIST 1.1) at 1 year between arms; ¿ To compare objective response rate (ORR; RECIST 1.1 and iRECIST) between arms; ¿ To compare Quality of Life (QoL) between arms; ¿ To evaluate the nature, severity, and frequency of toxicities between arms; ¿ To evaluate the incremental cost effectiveness and cost utility ratios between arms; ¿ To correlate the expression of tissue (including PD-L1) and blood markers with outcomes and response.;Primary end point(s): overall survival ;Timepoint(s) of evaluation of this end point: Death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): La risposta deve essere valutata mediante ripetizione di una TC torace e addome con m.d.c. dopo 6 e 12 settimane dalla randomizzazione e ogni 12 settimane successivamente, fino al termine del trattamento, 4 settimane dopo il completamento del trattamento, ogni 12 settimane successivamente fino a progressione o recidiva, e ogni 24 settimane successivamente fino al decesso. ; La risposta deve essere valutata mediante ripetizione di una TC torace e addome con m.d.c. dopo 6 e 12 settimane dalla randomizzazione e ogni 12 settimane successivamente, fino al termine del trattamento, 4 settimane dopo il completamento del trattamento, ogni 12 settimane successivamente fino a progressione o recidiva, e ogni 24 settimane successivamente fino al decesso.; La qualit¿ di vita viene valutata mediante la somministrazione dei questionari EORTC QLQ-C30 (versione 3.0) e QLQ-LC13, alla visita basale (prima della randomizzazione), al giorno 1 di ogni ciclo, 4 settimane dopo il completamento della terapia in studio e ad ogni visita di follow-up successiva. ; Ogni 3 - 4 settimane; La valutazione dell¿impatto finanziario e dall¿impiego delle risorse economiche viene valutato mediante la somministrazione del questionario EQ-5D 5L, alla visita basale (prima della randomizzazione), al giorno 1 di ogni ciclo, 4 settimane dopo il completamento della terapia in studio e ad ogni visita di follow-up successiva. ; biomarcatori tissutali : screening biomarcatori circolanti: 1. Prima dell¿inizio del trattamento 2. Al giorno 1 del 4¿ ciclo 3. Al termine del trattamento ;Timepoint(s) of evaluation of this end point: Tumor assessments with CT scan will be performed at baseline, after 6 and 12 weeks from randomization, and every 12 weeks thereafter until the end of treatment, 4 weeks after the end of treatment, every 12 weeks thwereafter until progression, and every 24 weeks thereafter until death.; Tumor assessments with CT scan will be performed at baseline, after 6 and | — |
Countries
Canada, Italy
Contacts
Public ContactUnit¿ Sperimentazioni Cliniche
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Outcome results
None listed