A Study of Nivolumab and Chemotherapy Followed by Surgery for Mesothelioma

Study Overview
=================
Brief Summary
-----------------
This study will test whether giving nivolumab in combination with pemetrexed and either cisplatin or carboplatin before surgery is a safe and effective approach to treating resectable mesothelioma without delaying surgery.

Official Title
-----------------
Feasibility and Safety of Neoadjuvant Nivolumab and Chemotherapy for Resectable Malignant Pleural Mesothelioma

Conditions
-----------------
Malignant Pleural Mesothelioma

Intervention / Treatment
-----------------
* Drug: Nivolumab
* Drug: Pemetrexed
* Drug: Cisplatin or Carboplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥ 18 years Karnofsky performance status > 70% Pathologic diagnosis of malignant pleural mesothelioma. Potentially resectable by pleurectomy/decortication, as assessed by thoracic surgeon Negative serum pregnancy test in women of childbearing potential Female patients of childbearing potential must agree to use a highly effective form of contraception for the duration of the study and for at least 5 months after the last administration of nivolumab and at least 6 months after last administration of pemetrexed, whichever is longer Male patients with female partners of childbearing potential must agree to use a highly effective form of contraception for the duration of the study and for at least 7 months after the last administration of nivolumab and at least 3 months after the last administration of pemetrexed, whichever is longer Adequate archival or fresh tissue for correlative analysis. Archival tissue will be deemed acceptable as long as their was no interval therapy prior to cycle 1 day 1 of protocol therapy. If sufficient archival or fresh tissue is not available, then a repeat biopsy at baseline prior to starting study treatment will be required as long as medically safe and feasible Absolute neutrophil count ≥ 1000/mcL Total bilirubin ≤ 1.5 mg/dl AST and ALT ≤ 3.0 x upper limit of normal Creatinine ≤ 1.5 x upper limit of normal Negative HIV serology blood test Exclusion Criteria: Prior treatment with chemotherapy or immunotherapy for mesothelioma Autoimmune disease requiring systemic immune modulating treatment during the past two years Pregnant or lactating women Known active hepatitis B or hepatitis C Current use of systemic prednisone at dose ≥ 10 mg daily (or the equivalent dose with another corticosteroid) Serious concurrent medical illness or another active cancer requiring treatment Active pneumonitis

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a single institution pilot study of nivolumab with pemetrexed and cisplatin or carboplatin prior to surgery for patients with potentially resectable malignant pleural mesothelioma (MPM).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nivolumab with pemetrexed and cisplatin or carboplatin<br>Eligible patients will receive two cycles of neoadjuvant therapy with nivolumab 360 mg, pemetrexed 500 mg/m2, and cisplatin 75 mg/m2 or carboplatin AUC=5. Subsequently, they will undergo pleurectomy/decortication. | Drug: Nivolumab<br>* nivolumab 360 mg<br>Drug: Pemetrexed<br>* 500 mg/m^2<br>Drug: Cisplatin or Carboplatin<br>* cisplatin 75 mg/m2 or carboplatin AUC=5<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of patients going to operating room for surgical resection | Patients who experience a greater than 30 day toxicity induced delay of surgery will be counted as a failure for the primary feasibility endpoint. | 30 days of the initially planned date | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nivolumab, Surgery, Pemetrexed, Cisplatin, Carboplatin, 19-272