Phase 2 Evaluation of Multi-modality Algorithm for Non-metastatic Adenocarcinoma of Pancreas or Ampulla

Phase 2 Evaluation of a Community-Based Multi-modality Management Algorithm for Clinically Non-metastatic Ductal Adenocarcinoma of the Exocrine Pancreas or Ampulla

Patients diagnosed with pancreatic cancer without clinically detectable metastatic disease will be treated with standardized systemic chemotherapy, followed by chemoradiation, and then surgical resection for those with resectable or borderline resectable disease. The primary endpoint is disease-free survival at 1 yr from initiation of treatment.

Study Overview

• Status: Terminated
• Conditions: Ductal Adenocarcinoma of Pancreas; Adenocarcinoma of Ampulla
• Intervention / Treatment: Drug: Gemcitabine and nanoparticle albumin bound paclitaxel; Procedure: Definitive resection; Drug: 5-fluorouracil and irinotecan; Radiation: Preoperative chemoradiation

Detailed Description

Patients with ductal adenocarcinoma of the pancreas (or ampulla) that have received no prior therapy and have no clinically detectable metastatic disease will be enrolled. Management will be driven by resectability status as defined by the American College of Surgeons. All patients will be defined at entry as Resectable, Borderline Resectable or Locally Advanced (Unresectable).

All patients will be treated initially with gemcitabine and nanoparticle albumin bound paclitaxel (nab-paclitaxel) every 14 days for 4 cycles. Patients classified as Resectable, who have CA19-9 below 180 and CA-125 below 30 will then proceed to resection. All other patients will get 5-fluorouracil as 46 hr infusion given with leucovorin and irinotecan (FOLFIRI-3) every 14 days x 4 cycles.

All patients without progression will then receive chemoradiation consisting of external beam radiotherapy (40 Gy in 20 fractions given over 4 weeks). During radiation all patients will receive radiosensitizing radiotherapy as: 5-fluorouracil at 225 mg/m2 5 days per week, Mitomycin-C at 3 mg.m2 on d1, 8, 15 & 22; Cisplatin at 10 mg/m2 on d2, 9, 16, 23 and unfractionated heparin at 6,000 units/m2 daily in divided doses from day 1 to day 28.

After approximately 4 weeks to recover from chemoradiation, all patients with Resectable or Borderline Resectable disease will undergo definitive surgery.

Adjuvant therapy with FOLFIR-3 for an additional 6 cycles will be offered to all patients post-operatively.

Patients will then be actively followed every 3 to 6 months in keeping with National Comprehensive Cancer Network (NCCN) guidelines for 2 yrs, and then followed for recurrence, late toxicity and vital status every 6 months through 5 years.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Duluth, Minnesota, United States, 55805
      • Essentia Health Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologic proof of adenocarcinoma consistent with ductal carcinoma of pancreas or ampulla, with no evidence of metastatic disease by clinical exam or cross-sectional imaging.
• Fitness for chemotherapy in judgement of treating physician
• Bilirubin < 4 (any means of biliary drainage acceptable)

Exclusion Criteria:

• Medical or mental illness precluding provision of informed consent
• Pregnancy
• Active infection for which neutropenia would pose high risk of mortality

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Resectable, Low Risk; Systemic chemotherapy followed by definitive surgery without pre-operative or post-operative radiotherapy.	Drug: Gemcitabine and nanoparticle albumin bound paclitaxel; Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles; Other Names: Gem/Abraxane, Gemcitabine/nab-paclitaxel; Procedure: Definitive resection; Definitive surgical resection of primary tumor; Other Names: pancreaticoduodenectomy, Whipple procedure
Experimental: Locally Advanced; Systemic chemotherapy followed by chemoradiation, followed by definitive surgery	Drug: Gemcitabine and nanoparticle albumin bound paclitaxel; Gemcitabine and nab-paclitaxel given every 14 days x 4 cycles; Other Names: Gem/Abraxane, Gemcitabine/nab-paclitaxel; Procedure: Definitive resection; Definitive surgical resection of primary tumor; Other Names: pancreaticoduodenectomy, Whipple procedure; Drug: 5-fluorouracil and irinotecan; FOLFIRI.3 given every 14 days x 4 cycles; Other Names: FOLFIRI.3, FOLFIRI-3; Radiation: Preoperative chemoradiation; Pre-operative chemoradiation to 40 Gy in 20 fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse Free Survival	Percentage of patients alive and free of detectable disease 1 yr from start of treatment	1 yr form onset of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R-0 Rate	Rate of patients having surgery who have negative surgical margins (i.e. R-0 resection)	Time of surgery
Overall Survival	Time to death from any cause measured from start of treatment	Up to 3 years from registration

Collaborators and Investigators

• Sponsor: Essentia Health
• Investigators: Principal Investigator: Peter Kebbekus, MD, PhD, Essentia Health Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2016
• Primary Completion (Actual): September 20, 2016
• Study Completion (Actual): September 14, 2017

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 8, 2015
• First Posted (Estimate): December 10, 2015

Study Record Updates

• Last Update Posted (Actual): November 13, 2018
• Last Update Submitted That Met QC Criteria: October 12, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Carcinoma; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase Inhibitors; Topoisomerase I Inhibitors; Gemcitabine; Paclitaxel; Fluorouracil; Irinotecan; Albumin-Bound Paclitaxel
• Other Study ID Numbers: PANC-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We will make unidentified dataset available for electronic download.

Study Data/Documents

1. Study Protocol