Non- Small-Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10025122 Term: Lung squamous cell carcinoma stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Durvalumab
Product Code: [MEDI4736]
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Durvalumab
Current Sponsor code: Durvalumab
Concentration unit: mg/l m
Sponsors
FONDAZIONE RICERCA TRASLAZIONALE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adequate normal organ and marrow function as definedbelow: -Haemoglobin = 9.0g/dL -Absolute neutrophil count (ANC)1.0 x109/L -Platelet count = 100 x 109/L -Serum bilirubin = 1.5 x institutional upper limit of normal(ULN). -AST (SGOT)/ALT (SGPT) =2.5 x institution a lupper limit of normal unless liver metastases are present, in which case it must be =5xULN -Measured creatinine clearance (CL)> 40mL/minor Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24- hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140–Age) x 0.85 72 x serum creatinine (mg/dL) Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Women who are surgically sterile (ie, bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) are eligible. The following age specific requirments apply: - Women 1year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy orhysterectomy). 3. Histological or cytological confirmed diagnosis of advanced or metastatic NSCLC with no evidence of EGFR mutations or ALK rearrangement. 4. Previous platinum-based chemotherapy. Only one line of previous chemotherapy is allowed. Adjuvant or neoadjuvant chemotherapy is not considered a line of therapy if completed at least 6 months before trial inclusion 5. Age > 18 years at time of studyentry. 6. Performance Status 0-1(ECOG) 7. Body weight>30kg 8. Able of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 9. Patient 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. 10. Must have a life expectancy of at least 12weeks 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 42 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 42
Exclusion criteria
Exclusion criteria: 1. Participation in another clinical study with an investigational product 2. Concurrent enrolment in another clinical study 3. Any previous treatment with a checkpoint inhibitor 4. History of another primary malignancy except for: • Malignancy treated with curative intent and with no known active disease =5 years before the first dose of study drug and of low potential risk for recurrence • Adequately treated non-melanoma skin cancer or lentigomaligna without evidence ofdisease • Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer insitu. 5. Receipt of the last dose of anticancer therapy 21 days prior to the first dose of study drug 6. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions: - Intranasal, inhaled, topical steroids, or local steroid injections - Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent - Steroids as premedication for hypersensitivity reactions 7. Any unresolved toxicity NCI CTCAE Grade =2 from previous anticancer therapy - Patients with Grade =2 neuropathy will be evaluate donacase-by-case basis after consultation with the StudyPhysician. - Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab may be included only after consultation with the Study Physician. 8. Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable. 9. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug 10. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP.Note:Local surgery of isolated lesions for palliative intent is acceptable. 11. History of allogenic organt ransplantation. 12. 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], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion: - Patients with vitiligo oralopecia - Patients with hypothyroidism stable on hormone replacement - Any chronic skin condition that does not require systemic therapy - Patients without active disease in the last 5 years may be included but only after consultation with the study physician - Patients with celiac disease controlled by diet alone 13. Uncontrolled intercurrent illness 14. History of leptomeningeal carcinomatosis 15. History of active primary immune deficiency 16. Active infection including tuberculosis,hepatitis B, hepatitis C,or human immunodeficiency virus. 17. Receipt of live attenuated vaccine within 30 days prior to the first dose of IP 18. Female patients who are pregnant or breastfeeding 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. 19. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 20. Prior randomisation or treatment in a previous durvalumab clinical study re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess whether concomitant administration of corticosteroids (10 mg/day of prednisone equivalent) reduces incidence of side effects without affecting response to durvalumab therapy in pretreated advanced or metastatic NSCLC as measured by ORR.;Secondary Objective: - To evaluate the clinical impact of the combined (durvalumab + prednisone) treatment in terms of overall survival (OS) and progression free survival (PFS) - To investigate the association with tumor biomarkers in tumor tissue or blood, including PD-L1 expression, tumor grading and tumor mutational burden (TMB) - To evaluate the clinical impact of the combined (durvalumab + prednisone) treatment in terms of overall survival (OS) according to presence of bone and liver metastases;Primary end point(s): a)objective response rate (ORR), for the assessment of efficacy b)incidence of immune-related side effects: for the assessment of safety;Timepoint(s) of evaluation of this end point: Disease assessments will be performed every 8 weeks. Therapy will be given until disease progression, unacceptable toxicity or patient refusal. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall survival rate (OS); Progression free survival rate (PFS); Biomarker analyses, which will be conducted on archival tumor tissue (TT) collected prior to trial therapy and on blood samples collected at enrolment and at disease progression. Biomarker analyses, which will be conducted on archival tumor tissue (TT) collected prior to trial therapy on enrolled patients. Biomarkers include PD-L1 expression, tumor grading and tumor mutational burden (TMB). Archival TT were tested for PD- L1 in local or central Lab according to Center facilities and using one of the approved immunohistochemistry (IHC) platform. Tumor tissue (paraffin-embedded blocks or at least five 10-micron slices) collection will be mandatory for tumor grading and tumor mutational burden (TMB) assessment. Tumor grading and its association with PD-L1 expression and drug efficacy will beassessed.;Timepoint(s) of evaluation of this end point: Disease assessments will be performed every 8 weeks. Therapy will be given until disease progression, unacceptable toxicity or patient refusal.; Disease assessments will be performed every 8 weeks. Therapy will be given until disease progression, unacceptable toxicity or patient refusal.; Disease assessments will be performed every 8 weeks. Therapy will be given until disease progression, unacceptable toxicity or patient refusal. | — |
Countries
Italy
Contacts
Public ContactCRO
Clinical Research Technology
Outcome results
None listed