Malignant Pleural Mesothelioma
Conditions
Keywords
progressive disease after at least 1 course of chemotherapy
Brief 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.
Detailed description
Patients will undergo pre- and post-treatment thoracoscopies/biopsies.
Interventions
DRUGnivolumab
Sponsors
Bristol-Myers Squibb
The Netherlands Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| DCR | at 12 weeks | The number of patients that have CR or PR plus the number of patients that have SD, as a percentage of the total number of patients in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PFS | Until progression, every 6 weeks up to 24 weeks. | The time from the date of start of treatment to the date of the first documented tumor progression as determined by modified RECIST, or death due to any cause. |
| OS | every 8 weeks until death | The time from date of start of treatment to the date of death |
| TTP | Until progression, every 6 weeks up to 24 weeks. | The time from the date of start of treatment to the time of disease progression. |
| Safety and tolerability (The incidence of (serious) adverse events) | Participants will be followed fot the duration of the trial, an expected average of 6 weeks | The incidence of (serious) adverse events |
| DCR | At 6 months | The number of patients that have CR or PR plus the number of patients that have SD, as a percentage of the total number of patients in the study. |
| ORR | Every 6 weeks up to 24 weeks. | The number of subjects whose best confirmed objective response is a CR or PR, divided by the number of treated subjects. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory | At screening and after cycle 3 (day 35-50) | The effects of nivolumab on tissue samples with respect to influx of immuno-modulating cells and the PD-L1 status of tumors and other possible biomarkers and explore correlations between biomarkers and anti-tumor activity. |
Outcome results
None listed