Preoperative mFOLFIRINOX (or Gem-Nab-P) +/- Isotoxic High-dose SBRT for Borderline Resectable Pancreatic Adenocarcinoma

Launched by ERASME UNIVERSITY HOSPITAL · Oct 15, 2021

Keywords

ClinConnect Summary

This clinical trial is investigating whether adding a specific type of high-dose radiation therapy, called isotoxic high-dose stereotactic body radiotherapy (iHD-SBRT), to chemotherapy before surgery can help patients with borderline resectable pancreatic cancer. The goal is to improve the chances of successful surgery and overall survival. Participants will receive either a combination of two chemotherapy regimens (mFOLFIRINOX or Gem-Nab-P) along with the iHD-SBRT, and researchers will closely monitor the effects of this treatment approach.

To be eligible for this trial, participants must be at least 18 years old and have a confirmed diagnosis of pancreatic adenocarcinoma that is considered borderline resectable. They should not have received any prior chemotherapy or radiation for their pancreatic cancer and must meet specific health criteria, such as having good blood counts and no significant nerve damage. Participants can expect to undergo several rounds of chemotherapy, followed by the radiation treatment, before being evaluated for surgery. It’s essential for potential participants to discuss their specific situation with their doctor to see if they qualify and to understand what being part of the trial would involve.

Gender

ALL

Eligibility criteria

• Inclusion criteria:
• • Cytologic or histologic proof of adenocarcinoma of the pancreatic head or uncinated process or body or tail. Diagnosis should be verified by local pathologist
• • cTNM stage: T1-4N0-2M0
• • Confirmation of clinical and radiographic stage as borderline resectable (CT scan and/or MRI scan with contrast according to the NCCN criteria) by a multidisciplinary board, composed by a dedicated oncological surgeon, radiologist and GI oncologist)
• • Age \> 18 years old
• • No prior chemotherapy or radiation for pancreatic cancer
• • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• • No grade ≥ 2 neuropathy
• * Laboratory parameters as follows:
• • Absolute neutrophil count (ANC) ≥ 1,500/mm³
• • Platelet count ≥ 100,000/mm³
• • Hemoglobin ≥ 9 g/dL
• • Creatinine ≤ 1.5 x upper limit of normal (ULN) or estimated GFR \>45 mL/min
• • Bilirubin ≤ 1.5 x ULN, including after adequate biliary stenting with metal stent (ideally 4 cm length)
• • Aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5x ULN
• • CA 19.9 \< 2500 kU/l (baseline, prior to any therapy and absence of cholestasis)
• Exclusion Criteria:
• • Evidence of extrapancreatic disease on diagnostic imaging (CT, MRI or PET scan), histologically proven or at laparoscopy, including distal nodal involvement beyond the peripancreatic tissues (including non-regional lymph node involvement, ie: proven involvement of precaval lumbar lymphadenopathy(ies) and/or distant metastases
• • Locally advanced disease as defined by the NCCN criteria (version 2.2021) ie \> 180° arterial encasement (SMA and CA) unreconstructible venous encasement (SMV/PV) due to tumor involvement or occlusion of a long segment.
• • CA 19.9 \> 2500 kU/l (baseline and absence of cholestasis)
• • Contraindication of surgery (general)
• • Contraindications to receive FFX or gemcitabine-nab-Paclitaxel
• • History of radiotherapy of the upper abdomen
• • Prior treatment with oxaliplatin, irinotecan, fluoruouracil or capecitabin
• • Patient \< 18 years old
• • Major surgery within 4 weeks of study entry
• • Uncontrolled pre-existing disease including, but not limited to: active infection, symptomatic congestive heart failure, unstable angina, social / psychiatric disorder that would limit compliance to treatment and good understanding of the informed consent form
• • Other concurrent anticancer therapies
• • Existence of another active neoplasia other than basal cell carcinoma of the skin, cervical carcinoma in situ or non-metastatic prostate cancer. Patients who have a history of neoplasia must have been in remission for more than 5 years to be included in the protocol
• • Pregnant or breastfeeding women; for women of childbearing potential only, a negative pregnancy test done \< 7 days prior to registration is required. Using of reliable contraception for at least 1 month before treatment is mandatory
• • Chronic concomitant treatment with strong inhibitors of cytochrome p450, family 3, subfamily a, polypeptide 4 gene (CYP3A4) is not allowed on this study; patients on strong CYP3A4 inhibitors must discontinue the drug for 14 days prior to registration on the study
• Additional exclusion criteria before randomisation:
• • Progressive disease (RECIST or PETCT, including non locoregional nodal involvement and increase of CA 19.9 by 20%) after receiving 4 cycles of FFX (or G/NP), including shift chemotherapy in case of early progression.
• • CA 19.9 \> 1000 kU/l after neoadjuvant therapy.
• • Presence of unmanageable toxicity during the first part of neoadjuvant chemotherapy (first 4 cycles or 6 doses of FFX or G/NP, respectively.
• • Pancreatic tumour \> 7.0 cm in greatest axial dimension at the time of randomization
• • Massive invasion of the stomach or intestines and/or direct intestinal invasion of the mucosae visible at ultrasoundendoscopy
• • Active gastric or duodenal ulcer disease at the time of randomization. Tolerated in case of antecedent without active ulcer (confirmation by endoscopy before iHD-SBRT)