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

NCT ID: NCT04156087

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-09
• Study Completion Date: 2024-01-29

Brief 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.

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)

Conditions

Pancreatic Cancer Non-resectable

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MIMIPAC

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

Group Type: EXPERIMENTAL

Durvalumab 50 MG/ML

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Minimally Invasive Surgical Microwave Ablation (MIS-MWA)

Intervention Type: PROCEDURE

Minimally invasive surgical microwave ablation (MIS-MWA) of the pancreatic tumor will be performed two weeks after the first dose of Durvalumab and Tremelimumab

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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

Intervention Type: PROCEDURE

Other Intervention Names

MEDI4736; IMFINZI; Gemzar

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

Baki Topal

OTHER

Sponsor Role: lead

Responsible Party

Baki Topal

Professor, Doctor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Baki Topal, MD

Role: PRINCIPAL_INVESTIGATOR

UZ Leuven

Locations

University Hospitals KU Leuven

Leuven, Vlaams-Brabant, Belgium

Countries

Belgium

Other Identifiers

2018-002852-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UZ S61508

Identifier Type: -

Identifier Source: org_study_id