Nivolumab in Patients With Recurrent Malignant Mesothelioma

NCT02497508 | Completed Phase 2 DMC

• 1 other identifier: N14MPN
• Study Type: interventional
• Target: 33
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Malignant Pleural Mesothelioma

Keywords

progressive disease after at least 1 course of chemotherapy

Outcome Measures

Primary Outcomes (1)

• DCR

  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.

  at 12 weeks

Secondary Outcomes (6)

• PFS

  Until progression, every 6 weeks up to 24 weeks.

• OS

  every 8 weeks until death

• TTP

  Until progression, every 6 weeks up to 24 weeks.

• ORR

  Every 6 weeks up to 24 weeks.

• 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

Other Outcomes (1)

• Exploratory

  At screening and after cycle 3 (day 35-50)

Study Arms (1)

Nivolumab

EXPERIMENTAL

Nivolumab will be administered 2 weekly by intravenous infusion in a dose of 3 mg/kg

Drug: nivolumab

Interventions

nivolumab DRUG

Also known as: BMS-936558

Nivolumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Bristol-Myers Squibb: collaborator

Related Publications (1)

• Desai AP, Kosari F, Disselhorst M, Yin J, Agahi A, Peikert T, Udell J, Johnson SH, Smadbeck J, Murphy S, Karagouga G, McCune A, Schaefer-Klein J, Borad MJ, Cheville J, Vasmatzis G, Baas P, Mansfield A. Dynamics and survival associations of T cell receptor clusters in patients with pleural mesothelioma treated with immunotherapy. J Immunother Cancer. 2023 Jun;11(6):e006035. doi: 10.1136/jitc-2022-006035.

  PMID: 37279993 DERIVED

MeSH Terms

Conditions

Mesothelioma, Malignant

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Mesothelioma; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Paul Baas, MD, PhD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

• Josine Quispel-Janssen, MD

  The Netherlands Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2015
• First Posted: July 14, 2015
• Study Start: July 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 1, 2017
• Last Updated: September 14, 2017

Record last verified: 2017-09