Progression-free Survival After MWA Plus Durvalumab and Tremelimumab for Unresectable Locally Advanced Pancreatic Cancer

Study Overview
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Brief Summary
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This phase-2 monocenter non-randomized prospective clinical trial evaluates the effectiveness of minimally invasive microwave ablation plus immunotherapy for unresectable non-metastatic locally advanced pancreatic cancer.

Detailed Description
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Research Hypothesis Does MIS-MWA combined with durvalumab (MEDI4736) plus tremelimumab and gemcitabine prolong progression-free survival in patients with unresectable non-metastatic adenocarcinoma of the pancreas? Investigational Product(s) and Reference Therapy: Combination of Durvalumab (fixed dose of 1500 mg) and Tremelimumab (fixed dose of 75 mg) will be given 2 weeks before surgery. Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab After 4 doses of Durvalumab and Tremelimumab, only Durvalumab 1500mg is provided q4w until disease progression. Systemic gemcitabine will be started 6 weeks after MIS-MWA. Gemcitabine will be given at a dose of 1000 mg /m² body surface, once a week for 3 weeks, followed with a week of rest. Objectives: Primary Objectives: Progression-free survival (PFS) Secondary Objectives: Safety: clinical and hematological toxicity (NCI CTCAE v. 5.0) of chemotherapy and immunotherapy Safety: number and type of postoperative complications of the MIS-MWA procedure Length of hospital stay Tertiary Objectives Overall survival (OS)

Official Title
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Progression-free Survival After Minimally Invasive Surgical Microwave Ablation Plus Durvalumab (MEDI4736) and Tremelimumab for Unresectable Non-metastatic Locally Advanced Pancreatic Cancer: MIMIPAC Trial

Conditions
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Pancreatic Cancer Non-resectable

Intervention / Treatment
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* Drug: Durvalumab 50 MG/ML
* Drug: Tremelimumab
* Drug: Gemcitabine
* Procedure: Minimally Invasive Surgical Microwave Ablation (MIS-MWA)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable non-metastatic Locally Advanced Pancreatic Cancer (LAPC) defined according to NCCN guidelines Version 2.2017 Histologically proven adenocarcinoma of the pancreas located in the head, body or tail LAPC tumor greatest diameter maximum 5 cm Male or female, age 18 years and older, ECOG PS 0-1 Life expectancy of at least 12 weeks Only patients who did not receive chemotherapy for their PC are allowed Patients without distant organ metastases on conventional diagnostic imaging Pre-operative biliary drainage for obstructive jaundice is allowed, but the type of biliary stent is standardized in all jaundiced patients Patients fit for MIS-MWA Able to receive Durvalumab and Tremelimumab. Patients with good liver and renal function and with good hematology Effective contraception for both male and female patients if applicable. Women of childbearing potential must have negative blood pregnancy test at screening visit. Written informed consent (+ optional for TR) must be given according to ICH/GCP and national/European regulations Exclusion Criteria: Pregnancy Metastatic PC on conventional diagnostic imaging or staging laparoscopy LAPC tumor greatest diameter is larger than 5 cm Borderline or resectable PC defined according to the NCCN guidelines version 2.2017 Systemic chemo(radio)therapy is not allowed before MIS-MWA Major surgical procedure within 28 days prior to the first dose of investigational products Classic contraindications for PDL and CTLA antibodies

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIMIPAC<br>Intervention: MIS-MWA plus immunotherapy using the combination of durvalumab with tremelimumab | Drug: Durvalumab 50 MG/ML<br>* Combination of Durvalumab (fixed dose of 1500 mg) and Tremelimumab (fixed dose of 75 mg) will be given 2 weeks before surgery. Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab After 4 doses of Durvalumab and Tremelimumab, only Durvalumab 1500mg is provided q4w until disease progression. Systemic gemcitabine will be started 6 weeks after MIS-MWA. Gemcitabine will be given at a dose of 1000 mg /m² body surface, once a week for 3 weeks, followed with a week of rest.<br>* Other names: IMFINZI;Drug: Tremelimumab<br>* Combination of Durvalumab (fixed dose of 1500 mg) and Tremelimumab (fixed dose of 75 mg) will be given 2 weeks before surgery. Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab After 4 doses of Durvalumab and Tremelimumab, only Durvalumab 1500mg is provided q4w until disease progression. Systemic gemcitabine will be started 6 weeks after MIS-MWA. Gemcitabine will be given at a dose of 1000 mg /m² body surface, once a week for 3 weeks, followed with a week of rest.<br>Drug: Gemcitabine<br>* Combination of Durvalumab (fixed dose of 1500 mg) and Tremelimumab (fixed dose of 75 mg) will be given 2 weeks before surgery. Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab After 4 doses of Durvalumab and Tremelimumab, only Durvalumab 1500mg is provided q4w until disease progression. Systemic gemcitabine will be started 6 weeks after MIS-MWA. Gemcitabine will be given at a dose of 1000 mg /m² body surface, once a week for 3 weeks, followed with a week of rest.<br>* Other names: Gemzar;Procedure: Minimally Invasive Surgical Microwave Ablation (MIS-MWA)<br>* Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | The study is exploratory and cannot be statistically powered for comparisons. Median progression-free survival (PFS) time is chosen as the clinically meaningful outcome. Survival estimates will be calculated using the Kaplan-Meier method. For information, the reference PFS time in patients with non-metastatic LAPC treated with gemcitabine monotherapy is about 6 months. Results will be presented descriptively. | 12 months |