Pancreatic Cancer Non-resectable
Conditions
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)
Interventions
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.
DRUGTremelimumab
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.
DRUGGemcitabine
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.
PROCEDUREMinimally 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
Sponsors
AstraZeneca
Baki Topal
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium
Outcome results
None listed