A Phase III, Randomized, Open Label Trial of Nivolumab in combination with Ipilimumab versus Pemetrexed with Cisplatin or Carboplatin as First Line Therapy in unresectable Pleural Mesothelioma
- Conditions
- MesotheliomaUnresectable10035597
- Registration Number
- NL-OMON47222
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 18
-Male and female subjects (18 years of age and over).
-Histologically proven diagnosis of (MPM), thoracoscopy is highly recommended.
-Advanced unresectable disease that is not amenable to therapy with curative intent (surgery with or without chemotherapy). Subjects that refuse potentially curative surgery are ineligible.
-Available (archival and/or fresh) pathological samples for centralized PD-L1 IHC testing during the screening period. Subjects cannot be randomized until the tumor tissue for PD-L1 testing has been received at the Central Lab, however, the result of the testing is not required prior to randomization. Subjects can initiate therapy before the result of PD-L1 testing is available.
-Prior palliative radiotherapy is acceptable, but at least 14 days must have passed since the administration of the radiotherapy and all signs of toxicity must have remitted.
-ECOG Performance Status of 0-1
-Weight loss < 10% during last 3 months
-Measurable disease, defined as at least 1 lesion measured in up to two positions at three separate levels on transverse cuts of CT scan that is suitable for repeated assessment using adapted modified Response Evaluation Criteria in Solid Tumors [m-RECIST] for pleural mesothelioma
-Adequate hematological, renal and hepatic functions
-Primitive peritoneal, pericardial and tunica vaginalis testis mesotheliomas
-Brain metastasis, except if surgically resected or treated with stereotaxic radiotherapy with no evolution within the 3 months before inclusion, and asymptomatic. In addition, subjects must be either off corticosteroids, or on a stable or decreasing dose of <=10 mg daily prednisone (or equivalent) for at least 2 weeks prior to randomization
-Prior treatment with adjuvant or neoadjuvant chemotherapy, radical pleuropneumonectomy with or without intensity modulated radiotherapy or non-palliative RT
-Prior intraoperative or intracavity chemotherapy for pleural mesothelioma
-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 checkpoint pathways.
-History of chronic inflammatory or autoimmune disease,
-Concurrent or prior malignancy requiring or anticipated to require concurrent intervention
-Subjects with interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Overall survival and the progression-free survival based on Blinded Independent<br /><br>Committee Review (BICR) assessment are the primary endpoints of the study.</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary Endpoints:<br /><br>*- Objective response rate (best overall response [BOR] is either a complete<br /><br>response [CR] or partial response [PR] per adapted m-RECIST and/or RECIST 1.1<br /><br>criteria<br /><br>*- Disease control rate (BOR is CR, PR, or stable disease [SD])<br /><br>*- PD-L1 expression level<br /><br><br /><br>Exploratory Endpoints:<br /><br>*- Incidence rates of adverse events, serious adverse events, deaths, and<br /><br>laboratory abnormalities<br /><br>*- Serum concentrations of nivolumab in combination with ipilimumab<br /><br>*- The improvement of the EuroWol Group*s self-reported health status measure<br /><br>(EQ-5D) and EQ Vas score<br /><br>*- Disease-related symptom improvement rate evaluated by mesothelioma adaption<br /><br>of Lung Cancer Symptom Scale (LCSS-Meso)</p><br>