Patients with Stage IIIB-not amenable to radical treatment or Stage IV metastatic or recurrent squamous-cell lung carcinoma (SqLC) MedDRA version: 21.0 Level: PT Classification code 10041826 Term: Squamous cell carcinoma of lung System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
FONDAZIONE RICERCA TRASLAZIONALE (FORT)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male and female patients willing and able to give written informed consent; 2) Histologically confirmed diagnosis of Stage IIIB-not amenable to radical treatment or Stage IV or recurrent squamous-cell lung carcinoma; 3) Tumor p63 (or p40) positive and TTF1 negative; 4) Availability of tumor tissue for PD-L1 expression analysis. One (1) formalin-fixed paraffin embedded tumor tissue block or a minimum of 16 unstained tumor tissue sections are acceptable. The tumor tissue sample may be fresh or archival if obtained within 6 months prior to enrollment, and there can have been no systemic therapy (eg, adjuvant or neoadjuvant chemotherapy) given after the sample was obtained. Tissue must be a core needle biopsy, excisional or incisional biopsy. Fine needle biopsies or drainage of pleural effusions with cytospins are not considered adequate for biomarker review. Biopsies of bone lesions that do not have a soft tissue component or decalcified bone tumor samples are also not acceptable; 5) Radiological measurable disease according to RECIST 1.1 criteria; 6) Chemonaive patient. Adjuvant/neoadjuvant chemotherapy is allowed if therapy was completed at least 6 months before trial inclusion; 7) Performance status 0-2 (ECOG); 8) Patient compliance to trial procedures; 9) Age = 18 years; 10) Written informed consent; 11) Adequate BM function (ANC = 1.5x109/L, Platelets = 100x109/L, HgB > 9g/dl); 12) Adequate liver function (bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 85
Exclusion criteria
Exclusion criteria: 1) No tumor tissue available; 2) Tumor negative for p63 (or p40) or positive for TTF1; 3) Absence of any measurable lesions; 4) Previous chemotherapy for stage IV disease; 5) Adjuvant or neoadjuvant chemotherapy completed less than 6 months before trial inclusion; 6) Concomitant radiotherapy or chemotherapy; 7) Previous radiotherapy on the target lesion(s). If all sites were included in radiotherapy fields patient is eligible only if there is evidence of progressive disease after completion of radiotherapy; 8) Untreated brain metastases; 9) Diagnosis of any other malignancy during the last 2 years, except for in situ carcinoma of cervix uteri and cutaneous squamous cell carcinoma; 10) Pregnancy or lactating; 11) Other serious illness or medical condition potentially interfering with the study. Nivolumab and ipilimumab specific exclusion: 1) Patients with an active, known or suspected autoimmune disease. Patients with type I diabetes mellitis; hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll; 2) 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 > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease; 3) Patients should be excluded if they are positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection; 4) Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the PFS rate of nivolumab plus ipilimumab with investigator’s choice chemotherapy in subjects with Stage IIIB-not amenable to radical treatment or Stage IV or recurrent squamous-cell lung carcinoma;Secondary Objective: Biomarker analysis;Primary end point(s): Progression-Free Survival (PFS) rate at 12 months;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Correlation of biomarkers with outcome to nivolumab plus ipilimumab therapy in terms of PFS, response rate (RR), overall survival (OS); 2) mPFS in all treated and in subgroups of biomarkers; 3) Overall RR in all treated and in subgroups of biomarkers; 4) OS in all treated and in subgroups of biomarkers; 5) Duration of response in all treated and in subgroups of biomarkers; 6) Safety; 7) Toxicity.;Timepoint(s) of evaluation of this end point: 48 months | — |
Countries
Italy
Contacts
Public ContactServizio Informazione sulla Sperime
Clinical Research Technology
Outcome results
None listed