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.
|First Received Date||July 6, 2015|
|Last Changed Date||February 27, 2017|
|Start Date||July 2015|
|Anticipated Primary Completion Date||July 2017|
|Primary Outcome Measures||
DCR [Time Frame: at 12 weeks]
|Secondary Outcome Measures||
PFS [Time Frame: Until progression, every 6 weeks up to 24 weeks.]
OS [Time Frame: every 8 weeks until death]
TTP [Time Frame: Until progression, every 6 weeks up to 24 weeks.]
ORR [Time Frame: Every 6 weeks up to 24 weeks.]
Safety and tolerability (The incidence of (serious) adverse events) [Time Frame: Participants will be followed fot the duration of the trial, an expected average of 6 weeks]
DCR [Time Frame: At 6 months]
|Study Arms / Comparison Groups||1 / 0|
Patients will undergo pre- and post-treatment thoracoscopies/biopsies.
|Recruitment Status||Active, not recruiting|
|Ages||18 Years - N/A|
|Accepts Healthy Volunteers||No|
- 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.
- 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
|Sponsor||The Netherlands Cancer Institute|
|Verification Date||February 2017|