Safety and Immunological Effect of Pembrolizumab in Resectable or Borderline Resectable Pancreatic Cancer

Study Overview
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Brief Summary
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The purpose of this clinical trial is to study an experimental drug called pembrolizumab or MK-3475 for use in combination with chemotherapy and radiation therapy for patients with resectable (surgical removal) or borderline resectable pancreatic cancer. In general, pancreatic cancer that cannot be removed by surgery is sometimes treated with chemotherapy and radiation therapy, called neoadjuvant treatment, to shrink the tumor so that surgery might be possible. However, this is not always effective at shrinking the tumor enough to allow it to be removed with surgery. Recent discoveries suggest that the investigators own immune system might have a role in controlling the growth of tumors. Drugs such as pembrolizumab can stimulate the immune system against cancer. The purpose of this study is to investigate whether pembrolizumab can be used safely during neoadjuvant treatment and can improve the body's immune response against pancreatic cancer. Pembrolizumab has been approved for treatment of patients with melanoma but has not been proven to be safe or helpful in patients with pancreatic cancer and is not approved by the U.S. Food and Drug Administration (FDA) for this purpose.

Official Title
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A Randomized Multicenter Ib/II Study to Assess the Safety & Immunological Effect of Chemoradiation Therapy in Combination With Pembrolizumab Compared to CRT Alone Resectable/Borderline Resectable Pancreatic Cancer

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: Pembrolizumab
* Radiation: Neoadjuvant Chemoradiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1. Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale Adequate organ function In subjects requiring biliary decompression, metal stent or drainage using percutaneous transhepatic cholangiogram (PTC) are allowed Exclusion Criteria: Immunodeficiency or taking steroid or any other form of immunosuppressive therapy Has a plastic biliary stent for decompression Metastatic disease Prior treatment for pancreatic cancer (other than 4-8 cycles of Folfirinox) or prior treatment with radiation for other diagnoses to the expected pancreatic cancer treatment area Active autoimmune disease Pregnancy or Nursing Known history of Human Immunodeficiency Virus (HIV) or Hepatitis B or C Prior monoclonal antibody within 4 weeks prior to study Day 1 Known additional malignancy that is progressing or requires active treatment Evidence of interstitial lung disease or active, non-infectious pneumonitis Active infection requiring systemic therapy Prior therapy with an anti-Program Death (PD-1) antibody, anti-PD-L1, anti-PD-L2, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neodjuvant CRT + Pembrolizumab<br>Standard neoadjuvant chemoradiation treatment (CRT) with pembrolizumab | Drug: Pembrolizumab<br>* Pembrolizumab administered at a dose of 200 mg IV every 3 weeks on days 1, 22, and 43 during concurrent neoadjuvant chemoradiation treatment<br>* Other names: Keytruda;Radiation: Neoadjuvant Chemoradiation<br>* Chemoradiation with capecitabine (825 mg/m2 orally twice daily, Monday through Friday, on days of radiation only) and radiation (50.4 Gy in 28 fractions over 28 days)<br>|
| Active Comparator: Neoadjuvant CRT<br>Standard neoadjuvant chemoradiation treatment (CRT) alone | Radiation: Neoadjuvant Chemoradiation<br>* Chemoradiation with capecitabine (825 mg/m2 orally twice daily, Monday through Friday, on days of radiation only) and radiation (50.4 Gy in 28 fractions over 28 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Tumor Infiltrating Lymphocytes (TILs) per high powered field (hpf) in pancreatic tissue (resected tissue). |  | 2-3 years | 
| Safety: Incidence of Dose-Limiting Toxicities (DLTs) |  | 2-3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival (DFS) |  | 2-4 years | 
| Overall survival (OS) |  | 2-4 years | 
| Response Rate (RR) |  | 2-3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunotherapy, Neoadjuvant, Resectable, Borderline resectable