Nivolumab in Patients With Recurrent Malignant Mesothelioma (NivoMes)

• ClinicalTrials.gov Identifier: NCT02497508
• Recruitment Status: Completed
• First Posted: July 14, 2015
• Last Update Posted: September 14, 2017
• Sponsor: The Netherlands Cancer Institute
• Collaborator: Bristol-Myers Squibb
• Information provided by (Responsible Party): The Netherlands Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malignant Pleural Mesothelioma	Drug: nivolumab	Phase 2

Detailed Description:

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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 Start Date: July 2015
• Actual Primary Completion Date: July 2017
• Actual Study Completion Date: July 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nivolumab; Nivolumab will be administered 2 weekly by intravenous infusion in a dose of 3 mg/kg	Drug: nivolumab; Other Name: BMS-936558

Outcome Measures

Primary Outcome Measures :

1. DCR [ Time Frame: 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 Outcome Measures :

1. PFS [ Time Frame: 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.
2. OS [ Time Frame: every 8 weeks until death ]
   The time from date of start of treatment to the date of death
3. TTP [ Time Frame: Until progression, every 6 weeks up to 24 weeks. ]
   The time from the date of start of treatment to the time of disease progression.
4. ORR [ Time Frame: 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.
5. 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 ]
   The incidence of (serious) adverse events
6. DCR [ Time Frame: 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.

Other Outcome Measures:

1. Exploratory [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Sponsors and Collaborators

The Netherlands Cancer Institute

Bristol-Myers Squibb

Investigators

• Principal Investigator: Paul Baas, MD, PhD; The Netherlands Cancer Institute
• Principal Investigator: Josine Quispel-Janssen, MD; The Netherlands Cancer Institute

More Information

• Responsible Party: The Netherlands Cancer Institute
• ClinicalTrials.gov Identifier: NCT02497508
• Other Study ID Numbers: N14MPN
• First Posted: July 14, 2015
• Last Update Posted: September 14, 2017
• Last Verified: September 2017

Keywords provided by The Netherlands Cancer Institute:

progressive disease after at least 1 course of chemotherapy

Additional relevant MeSH terms:

Mesothelioma; Mesothelioma, Malignant; 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; Nivolumab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action