Pancreatic Adenocarcinoma Neoadjuvant Chemotherapy Before Surgery

Official title

MFOLFIRINOX or Gemcitabine / Nab-paclitaxel Followed by Pancreatectomy for Patients with Borderline Resectable Pancreatic Adenocarcinoma. a Pilot Feasibility Study.

Overview

This is a single-arm, single-center feasibility trial of patients with borderline resectable pancreatic adenocarcinoma receiving chemotherapy with mFOLFIRINOX or gemcitabine / nab-paclitaxel followed by pancreatectomy.

Detailed description

Borderline resectable pancreatic adenocarcinoma infiltrates into adjacent vascular structures to an extent such that complete macroscopic resection is technically feasible, but an R0 resection poses a challenge when surgery is the primary therapy. Therefore, a different management strategy may be beneficial.

The primary outcome of the PANCREAS trial is defined as the proportion of eligible patients enrolled in the study over an 18-month period and the proportion of patients who complete the protocol (neoadjuvant therapy and pancreatectomy). Certain modifications of the neoadjuvant therapy protocol are expected and allowed, and the primary feasibility outcome will be one of the following: stop, main study non-feasible; continue with protocol modifications; or continue without modification. A safety analysis will be performed after first 15 patients are enrolled and complete neoadjuvant therapy and surgery. Patients enrolled in this trial will undergo interventions in the following order: neoadjuvant chemotherapy, re-staging CT scan, pancreatectomy and adjuvant chemotherapy. Postoperative mortality will be recorded up to 90 days after surgery. Patients will be followed every four months with a CT scan of the chest/abdomen for two years after resection or until evidence of disease recurrence. Patients who do not undergo surgical resection will be followed for two years after accrual (duration of study period) or until evidence of disease progression or death.

Interventions

• Drug mFOLFIRINOX
  mFOLFIRINOX, including: Oxaliplatin 85 mg/m2 IV over 2 hours, Leucovorin 400mg/m2 IV over 2 hours, Irinotecan at 150 mg/m2 IV over 90 min, 5-Fluoruracil continuous infusion of 2400 mg/m2 IV over 46h.
• Drug Gemcitabine / Nab-paclitaxel
  Both drugs are administered once weekly for three weeks (days 1, 8, 15) followed by a week of rest (28-day cycle) for 3 cycles prior to imaging. Gemcitabine: 1000 mg/m2 intravenous infusion over 30 to 40 minutes. Nab-paclitaxel: 125 mg/m2 intravenous infusion over 30 to 40 minutes.

Primary outcome measures

• Proportion of patients eligible enrolled [Time frame: 18 months]

Secondary outcome measures (4)

• Survival [Time frame: 24 months]
• Time to Progression [Time frame: 24 months from the initiation of chemotherapy (the length of the study)]
• Overall Complications from surgery [Time frame: From date of surgery (POD=0) up to 90 postoperative days (POD=90)]
• Pathological response to chemo-radiation treatment [Time frame: From the date of the first chemotherapy to the date of surgery (around 4 months)]

Eligibility criteria

Inclusion criteria

• 1\. Men and women 18 years of age or older who present with biopsy proven borderline resectable pancreatic adenocarcinoma who are medically fit for surgery as per assessment by treating surgeon.

2\. Age ≤ 79 years 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 4. Normal bone marrow and organ function

• Absolute neutrophil count (ANC) = or > 1500, platelets > 100K
• Total bilirubin <1.5x upper limit of normal (ULN)
• Alanine transaminase (ALT), Aspartate aminotransferase (AST) < 3 x ULN
• Creatinine <150umol/L
• Normal prothrombin time and international normalized ratio (INR) 5. Able to provide written informed consent

Exclusion criteria

• Proven metastatic disease (e.g. on imaging modality such as CT scan of the chest, abdomen and pelvis or MRI)
• Locally advanced pancreatic cancer (see definition section 3.3)
• Prior treatment with radiation therapy to the pancreas or associated field.
• Contraindications to receive chemotherapy
• History of cardiac disease including congestive heart failure (New York Heart Association class 2), active coronary artery disease or uncontrolled hypertension
• Concurrent ongoing systemic infections
• Illegal substance abuse, or social conditions that may interfere with patient's participation in the trial
• Pre-existing neuropathy
• Pregnant patients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Canada · 1 center

• Juravinski Hospital — Hamilton

Identifiers

NCT: NCT04452461 · 5076

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗