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

Pancreatic Cancer Non-resectable Clinical Trial

— MIMIPAC  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04156087
• Other study ID #: UZ S61508
• Secondary ID: 2018-002852-34
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 9, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2023
• Source: University Hospital, Gasthuisberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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)

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 12
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pancreatic Cancer Non-resectable
• Pancreatic Neoplasms

Intervention

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.
• 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.
• 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.

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

Locations

Country	Name	City	State
Belgium	University Hospitals KU Leuven	Leuven	Vlaams-Brabant

Sponsors (2)

Lead Sponsor	Collaborator
Baki Topal	AstraZeneca

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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