Nivolumab in Patients With Recurrent Malignant Mesothelioma

• Status: Completed
• Trial end date: 2017-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Netherlands Cancer Institute
• Collaborator: Bristol-Myers Squibb
• Treatments: Antibodies, Monoclonal; Nivolumab

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