Pancreatic Adenocarcinoma Neoadjuvant Chemotherapy Before Surgery

NCT ID: NCT04452461

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-01
• Study Completion Date: 2026-05-01

Brief 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.

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.

Conditions

Pancreatic Adenocarcinoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Arm Intervention

1. Chemotherapy: 6 cycles (three months) of IV combination chemotherapy with mFOLFIRINOX on day 1 followed by one week of rest (14-day cycle). Alternatively, patients will receive three months of gemcitabine / nab-paclitaxel.

2. Re-staging CT scan with Carbohydrate Antigen (CA) 19-9 serum test.

3. Staging laparoscopy to rule out occult metastatic disease is optional based on surgeon's preference.

5. Pancreatectomy 4 weeks following the last day of Chemotherapy as per standard of care.

6. Adjuvant chemotherapy: as per standard of care. 7. Clinical assessment and CT scan with CA 19-9 serum test at 4-month intervals until identification of cancer recurrence.

8. Follow up of patients after 2 years every six months for up to 5 years following the initiation of treatment will be performed off-protocol as per standard of care.

Group Type: OTHER

mFOLFIRINOX

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

5-FU; leucovorin; oxaliplatin; gemcitabine / abraxane

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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 79 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: lead

Responsible Party

Pablo Serrano

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leyo Ruo, MD

Role: PRINCIPAL_INVESTIGATOR

McMaster University

Locations

Juravinski Hospital

Hamilton, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Leyo Ruo, MD

Role: CONTACT

ruol@mcmaster.ca

905-521-2100 ext. 76626

Pablo E Serrano, MD

Role: CONTACT

serrano@mcmaster.ca

905-521-2100 ext. 43872

Facility Contacts

Leyo Ruo, MD

Role: primary

ruol@mcmaster.ca

905-521-2100 ext. 76626

Pablo E Serrano, MD

Role: backup

serrano@mcmaster.ca

905-521-2100 ext. 43872

Pablo E Serrano, MD

Role: backup

Brandon Meyers, MD

Role: backup

Christian van der Pol, MD

Role: backup

Tariq Aziz, MD

Role: backup

Sameer Parpia, PhD

Role: backup

Kimmen Quan, MD

Role: backup

Other Identifiers

5076

Identifier Type: -

Identifier Source: org_study_id