Nivolumab in Patients With Recurrent Malignant Mesothelioma (NivoMes)

Netherlands Cancer Institute (NKI)

Status and phase

Completed

Phase 2

Conditions

Malignant Pleural Mesothelioma

Treatments

Drug: nivolumab

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT02497508

N14MPN

Details and patient eligibility

About

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.

Full description

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

Enrollment

33 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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