Clinical trial NCT02497508: Nivolumab in Patients With Recurrent Malignant Mesothelioma
Official title: A Single Arm Phase II Study of Nivolumab in Patients With Recurrent Malignant Pleural Mesothelioma: Interim Biopsy Analysis to Determine Efficacy. Acronym: NivoMes Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Pleural Mesothelioma
Keywords: progressive disease after at least 1 course of chemotherapy
Lead sponsor: The Netherlands Cancer Institute
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2015-07-14
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: DCR
timeFrame: at 12 weeks
Secondary outcomes:
measure: PFS
timeFrame: Until progression, every 6 weeks up to 24 weeks.
measure: OS
timeFrame: every 8 weeks until death
measure: TTP
timeFrame: Until progression, every 6 weeks up to 24 weeks.
measure: ORR
timeFrame: Every 6 weeks up to 24 weeks.
measure: Safety and tolerability (The incidence of (serious) adverse events)
timeFrame: Participants will be followed fot the duration of the trial, an expected average of 6 weeks
measure: DCR
timeFrame: At 6 months
Other outcomes:
measure: Exploratory
timeFrame: At screening and after cycle 3 (day 35-50)
Locations:
Study officials:
affiliation: The Netherlands Cancer Institute
name: Paul Baas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Netherlands Cancer Institute
name: Josine Quispel-Janssen, MD
role: PRINCIPAL_INVESTIGATOR
References: