Malignant pleural mesothelioma MedDRA version: 19.0 Level: LLT Classification code 10027408 Term: Mesothelioma malignant advanced System Organ Class: 100000004864
Conditions
Sponsors
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Signed informed consent form • Age = 18 years • WHO-ECOG performance status 0 or 1 • Able to comply with the study protocol, in the investigator’s judgment • Patients with histologically confirmed diagnosis of the recurrence of MPM. Any pleural MPM subtype is permitted for inclusion in the study. • Progressive disease after at least one prior systemic treatment with a platinum-based doublet (both cisplatin and carboplatin are allowed) for unresectable MPM. All prior cytotoxic toxicities must have resolved to grade = 1 prior to registration • Measurable disease on CT scan, according to modified RECIST Criteria for Mesothelioma (Byrne MJ, 2004) • Life expectancy = 12 weeks • Adequate hematologic and organ function, defined by the following laboratory results, obtained within 14 days prior to the first study treatment: - Absolute neutrophil count (ANC) = 1500 cells/µL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1) - WBC count = 3000 cells/µL - Lymphocyte count = 250 cells/µL - Platelet count = 100.000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1) - Hemoglobin = 5.6 mmol/L - Serum albumin = 25 gr/L - AST, ALT and alkaline phosphatase = 2.5 x ULN, with the following exceptions: patients with documented liver or bone metastases: alkaline phosphatase = 5 x ULN - Serum bilirubin = 1.5 x ULN Patients with known Gilbert disease who have serum bilirubin level = 3 x ULN may be enrolled - INR and aPTT = 1.5 x ULN Patients receiving therapeutic anticoagulation should be on a stable dose - Creatinine clearance = 45 mL/min Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration or Modification of Diet in Renal Disease formulae may be used; 24-hour urine collection is not required • Women who are not postmenopausal (= 12 months of non-therapy-induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus) and men with partners of childbearing potential, must agree to use adequate contraception (double barrier birth control) for the whole duration of study treatment and for 3 months after the last dose of therapy • Women of childbearing potential must have a negative serum or urine pregnancy test within 48 hours prior the first dose of treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 16 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: • Medical or psychological impediment to comply with the protocol • Patients with only peritoneal MPM • Prior malignancy except adequately treated basal cell or squamous cell skin cancer, superficial or in-situ cancer of the bladder or other cancer for which the patient has been disease-free for at least five years • Concomitant participation in another clinical trial (by the investigator’s judgement) • Uncontrolled pleural/peritoneal effusion, pericardial effusion or ascites requiring recurrent drainage procedures (once monthly or more frequently) • Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy should be treated prior to enrolment. • Previous treatment with any checkpoint inhibitor • Pregnant or lactating women • Patients with brain metastases • History of or active autoimmune disease (e.g. pneumonitis; rheumatoid arthritis; severe form of psoriasis; uncontrolled type I diabetes or hypothyroidism) • History of idiopathic pulmonary fibrosis (including pneumonitis) or unresolved drug-induced pneumonitis, organizing pneumonia, or active pneumonitis on screening chest CT scan • History of relevant gastrointestinal disease, including, but not limited to, Crohn’s disease, ulcerative colitis, recurrent diverticulitis • Prior allogenic bone marrow transplantation or prior solid organ transplantation • History of HIV • Patients with history of HBV infection are eligible if serological profile is compatible with past/resolved infection (defined as negative HBsAg test and positive antibody to HBV core antigen [anti-HBc] antibody test) and HBsAg test and HBV-DNA are both negative prior to Cycle 1, Day 1 • Patients with history of HCV infection must be screened for HCV-RNA PCR test prior to Cycle 1, Day 1, and are eligible if the test turns negative • Other serious concomitant disease, including: - Active tuberculosis - Severe infections within 4 weeks prior to Cycle 1, Day 1 - Significant cardiovascular disease (NYHA class III or IV), myocardial infarction within the previous 6 months, unstable angina, or unstable arrhythmias - Significant pulmonary (asthma or COPD) or hepatic disease or other illness considered by the investigator to constitute an unwarranted high risk for investigational treatment • Major surgical procedures within 28 days prior to Cycle 1, Day 1 • Concurrent medications: - Treatment with systemic immunosuppressive medications, including but not limited to prednisone (with specific exceptions; see below), cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to Cycle 1, Day 1. - The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed. - The use of systemic prednisone at the dosage of 10 mg/day or lower (or equivalent) is allowed. • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is the disease control rate (DCR) at 12 weeks of the combination treatment of Nivolumab and Ipilimumab in patients with progressive MPM.;Secondary Objective: - to determine the safety profile of the combination treatment of Nivolumab plus Ipilimumab in patients with advanced MPM - to determine DCR at 6 months, PFS and OS in the study population - to determine objective response rate (ORR) as defined by modified RECIST criteria - to determine the immunological changes of tumors before and after 6 weeks of treatment. This research will include PD-L1 status and other possible biomarkers. ;Primary end point(s): DCR at 12 weeks;Timepoint(s) of evaluation of this end point: At 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PFS, OS, ORR, safety;Timepoint(s) of evaluation of this end point: PFS, ORR and OS: 6 weekly until week 48. Thereafter 12 weekly Safety: 2 weekly during treatment, thereafter every 6 weekly until week 48. Thereafter 12 weekly | — |
Countries
Netherlands
Contacts
Public ContactProf. Dr. P. Baas
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Outcome results
None listed