nivolumab in patients with recurrent malignant mesothelioma

Conditions: Malignant Pleural Mesothelioma

Summary: this is a prospective, single arm, phase ii trial in previously treated patients with mpm who are considered candidates for immunotherapy and repeat thoracoscopies/transthoracic biopsies. nivolumab will be administered 3 mg/kg q2 weeks by intravenous injection. the administration of nivolumab as monotherapy will improve dcr form 20% to 40% at 12 weeks when compared to dcr of patients treated with best supportive care based on historical controls.

patients will undergo pre- and post-treatment thoracoscopies/biopsies.

Eligibility criteria:
inclusion criteria: * patients with histological or cytological diagnosed malignant pleural mesothelioma and age \>18 years. * progressive disease after at least one course of chemotherapy. * previous chemotherapy or experimental therapy ≥ 4 weeks ago. * 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, the interval is \> 12 weeks and not all tumor is within the irradiation field. * who performance status 0 or 1 (see appendix 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 ≤ 1.5 times within the upper limits of normal (uln); asat and alat \<= 2.5x uln, ap (alkaline phosphatases) \< 5x uln (unless bone metastases are present in the absence of any liver disease). age and reproductive status * women of childbearing potential (wocbp) must use appropriate method(s) of contraception to avoid pregnancy during treatment and for 23 weeks after the last dose of investigational drug. * women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 iu/l or equivalent units of hcg) within 24 hours prior to the first dose of nivolumab. * men who are sexually active with wocbp must use any contraceptive method with a failure rate of less than 1% per year during treatment and for a period of 31 weeks after the last dose of investigational drug. * women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception. 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

Keywords: progressive disease after at least 1 course of chemotherapy