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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreatic Cancer Non-resectable
• Intervention / Treatment: Drug: Durvalumab 50 MG/ML; Drug: Tremelimumab; Drug: Gemcitabine; Procedure: Minimally Invasive Surgical Microwave Ablation (MIS-MWA)

Detailed Description

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)

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Vlaams-Brabant
    • Leuven, Vlaams-Brabant, Belgium, 3000
      • University Hospitals KU Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MIMIPAC; Intervention: MIS-MWA plus immunotherapy using the combination of durvalumab with tremelimumab

Drug: Durvalumab 50 MG/ML; 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.; Other Names: MEDI4736; IMFINZI; Drug: Tremelimumab; 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.; Drug: Gemcitabine; 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.; Other Names: Gemzar; Procedure: Minimally Invasive Surgical Microwave Ablation (MIS-MWA); Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Baki Topal
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Baki Topal, MD, UZ Leuven

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: November 5, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 7, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Durvalumab; Tremelimumab; Gemcitabine
• Other Study ID Numbers: UZ S61508; 2018-002852-34 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes