A single arm phase II study of Nivolumab in patients with progressive malignant pleural mesothelioma: interim biopsy analysis to determine efficacy. Acronym: NivoMes Study MedDRA version: 17.1 Level: LLT Classification code 10027408 Term: Mesothelioma malignant advanced System Organ Class: 100000004864
Conditions
Sponsors
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with proven malignant pleural mesothelioma, who have progressive disease after chemotherapy in first or second line. • Patients with histological or cytological diagnosed malignant pleural mesothelioma and age >18 years. • Medically suitable for limited surgical intervention (pleural biopsies up to limited pleurectomy). • Not considered candidates for trimodality treatment (as part of a study). • Measurable or evaluable disease (see tumor response assessment). • Ability to understand the study and give signed informed consent prior to beginning of protocol specific procedures including the approval of a second thoracoscopy or transthoracic pleural biopsy after the third course. • Radiotherapy is allowed when this is given for palliation of painful sites, the interval is > 12 weeks, not more than 1/3 of the bone marrow capacity or all tumor is within the irradiation field. • WHO performance status 0 or 1. • Adequate organ function as evidenced by the following peripheral blood counts or serum chemistries at study entry: • Hematology: Neutrophil count = 1.5 x 109/l, Platelets = 150 x 109/l, Hemoglobin = 6,0 mmol/l. • Chemistry: Total serum bilirubin within the upper normal limits; ASAT and ALAT = 2.5 times the upper limits of normal (ULN), AP (alkaline phosphatases) =65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: • Active uncontrolled infection, severe cardiac dysfunction or uncorrectable bleeding tendency. • Inability to perform biopsies of the pleural lesions. • Symptomatic peripheral neuropathy = grade 2 according to NCI CTC, version 4.0. • Presence of symptomatic CNS metastases. • Unstable peptic ulcer, unstable diabetes mellitus or other serious disabling condition. • Impaired renal function: creatinine clearance less than 50ml/min. • Concomitant administration to any other experimental drugs under investigation. • Patients are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger • Patients are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immuno-suppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses < 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. • Patients are excluded if they have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the DCR (disease control rate) at 12 weeks of nivolumab monotherapy in patients with progressive MPM. ;Secondary Objective: Secondary Objectives • To determine the safety of nivolumab monotherapy in patients with recurrent MPM • To determine the PFS, OS and TTP of nivolumab monotherapy • To determine the objective response rate (ORR) as defined by the modified RECIST criteria Exploratory Objectives • To determine the effects of nivolumab on tissue samples with respect to influx of immuno-modulating cells. • To determine the PD-L1 status of tumors and other possible biomarkers and explore correlations between biomarkers and anti-tumor activity.;Primary end point(s): DCR at 12 weeks.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety, PFS, OS, TTP, ORR;Timepoint(s) of evaluation of this end point: Safety: 2 weekly during treatment, thereafter every 6 weekly until week 24. Thereafter 8 weekly. PFS, TTP and ORR: 6 weekly until week 24. Thereafter 8 weekly OS: 8 weekly | — |
Countries
Netherlands
Contacts
Public ContactJ.M.M.F. Quispel-Janssen
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Outcome results
None listed