ivolumab in patients with progressive malignant pleural mesothelioma: NivoMes

• Conditions: 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: 17.1Level: LLTClassification code 10027408Term: Mesothelioma malignant advancedSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003935-20-NL
• Lead Sponsor: Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-01-15
• Last Update Posted: 7 December 2015

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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) < 5x ULN (unless bone metastases are present in the absence of any liver disease).

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 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the DCR (disease control rate) at 12 weeks of nivolumab monotherapy in patients with progressive MPM.<br><br>;Secondary Objective: Secondary Objectives<br>• To determine the safety of nivolumab monotherapy in patients with recurrent MPM<br>• To determine the PFS, OS and TTP of nivolumab monotherapy<br>• To determine the objective response rate (ORR) as defined by the modified RECIST criteria<br><br>Exploratory Objectives<br>• To determine the effects of nivolumab on tissue samples with respect to influx of immuno-modulating cells.<br>• 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 Outcome Measures

Name	Time	Method
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.<br>PFS, TTP and ORR: 6 weekly until week 24. Thereafter 8 weekly<br>OS: 8 weekly<br>