Pancreatic Adenocarcinoma Neoadjuvant Chemotherapy Before Surgery

Pancreatic Adenocarcinoma Clinical Trial

— PANCREAS  

Official title:

mFOLFIRINOX or Gemcitabine / Nab-paclitaxel Followed by Pancreatectomy for Patients With Borderline Resectable Pancreatic Adenocarcinoma. A Pilot Feasibility Study.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04452461
• Other study ID #: 5076
• Status: Recruiting
• Phase: Phase 2
• Start date: March 1, 2021
• Est. completion date: May 1, 2026

Study information

• Verified date: September 2023
• Source: Hamilton Health Sciences Corporation
• Contact: Leyo Ruo, MD
• Phone: 905-521-2100
• Email: ruol[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: May 1, 2026
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

1. Absolute neutrophil count (ANC) = or > 1500, platelets > 100K

2. Total bilirubin <1.5x upper limit of normal (ULN)

3. Alanine transaminase (ALT), Aspartate aminotransferase (AST) < 3 x ULN

4. Creatinine <150umol/L

5. Normal prothrombin time and international normalized ratio (INR) 5. Able to provide written informed consent

Exclusion Criteria:

1. Proven metastatic disease (e.g. on imaging modality such as CT scan of the chest, abdomen and pelvis or MRI)

2. Locally advanced pancreatic cancer (see definition section 3.3)

3. Prior treatment with radiation therapy to the pancreas or associated field.

4. Contraindications to receive chemotherapy

5. History of cardiac disease including congestive heart failure (New York Heart Association class 2), active coronary artery disease or uncontrolled hypertension

6. Concurrent ongoing systemic infections

7. Illegal substance abuse, or social conditions that may interfere with patient's participation in the trial

8. Pre-existing neuropathy

9. Pregnant patients

Related Conditions & MeSH terms

• Adenocarcinoma
• Pancreatic Adenocarcinoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Juravinski Hospital	Hamilton	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Hamilton Health Sciences Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients eligible enrolled	Over an 18-month period The proportion of patients who complete the protocol (neoadjuvant therapy and pancreatectomy). As described, there are certain modifications of the neoadjuvant therapy protocol that are expected and allowed. The primary feasibility outcome will be one of the following: Stop, main study non-feasible: 1) estimated proportion of eligible patients enrolled <40% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) <40%.; Continue with protocol modifications: 1) estimated proportion of eligible patients enrolled between 40-59% or 2) estimated proportion of enrolled patients who complete the protocol (neoadjuvant therapy and pancreatectomy) 40-59%.; Continue without modification: 1) estimated proportion of eligible patients enrolled equal to or greater than 60% or estimated proportion of enrolled patients who complete the protocol (neoadjuv	18 months
Secondary	Survival	Defined as percentage of patients alive at two years from enrolment.	24 months
Secondary	Time to Progression	Defined as the duration of time from enrolment to time to radiological evidence of disease progression or recurrence or death, whichever comes first.	24 months from the initiation of chemotherapy (the length of the study)
Secondary	Overall Complications from surgery	Occurrence of any postoperative complication (major or minor) from surgery following each patient's hospital stay and up to 90 days from the initial operation.	From date of surgery (POD=0) up to 90 postoperative days (POD=90)
Secondary	Pathological response to chemo-radiation treatment	Pathological response to treatment will be classified as per protocol.	From the date of the first chemotherapy to the date of surgery (around 4 months)