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

Phase 2
Active, not recruiting
Conditions
Pancreatic Cancer Non-resectable
Interventions
Procedure: Minimally Invasive Surgical Microwave Ablation (MIS-MWA)
Registration Number
NCT04156087
Lead Sponsor
Baki Topal
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)

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
12
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
MIMIPACDurvalumab 50 MG/MLIntervention: MIS-MWA plus immunotherapy using the combination of durvalumab with tremelimumab
MIMIPACMinimally Invasive Surgical Microwave Ablation (MIS-MWA)Intervention: MIS-MWA plus immunotherapy using the combination of durvalumab with tremelimumab
MIMIPACTremelimumabIntervention: MIS-MWA plus immunotherapy using the combination of durvalumab with tremelimumab
MIMIPACGemcitabineIntervention: MIS-MWA plus immunotherapy using the combination of durvalumab with tremelimumab
Primary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)12 months

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

University Hospitals KU Leuven

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Leuven, Vlaams-Brabant, Belgium

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