Phase 2 Evaluation Of Multi-modality Algorithm For Non-metastatic Adenocarcinoma Of Pancreas Or Ampulla

Study Overview

Phase 2 Evaluation of Multi-modality Algorithm for Non-metastatic Adenocarcinoma of 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.

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.

Ductal Adenocarcinoma of Pancreas
Adenocarcinoma of Ampulla

DRUG: Gemcitabine and nanoparticle albumin bound paclitaxel
DRUG: 5-fluorouracil and irinotecan
RADIATION: Preoperative chemoradiation
PROCEDURE: Definitive resection

PANC-1

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2015-12-03	Results First Submitted 2018-07-13	Last Update Submitted that met QC Criteria 2018-10-12
First Submitted that Met QC Criteria 2015-12-08	Results First Submitted that Met QC Criteria 2018-10-12	Last Update Posted (ACTUAL) 2018-11-13
First Posted (ACTUAL) 2015-12-10	Results First Posted 2018-11-13	Last Verified 2018-10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

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 PROCEDURE: Definitive resection Definitive surgical resection of primary tumor
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 DRUG: 5-fluorouracil and irinotecan FOLFIRI.3 given every 14 days x 4 cycles RADIATION: Preoperative chemoradiation Pre-operative chemoradiation to 40 Gy in 20 fractions PROCEDURE: Definitive resection Definitive surgical resection of primary tumor

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

PROCEDURE: Definitive resection

Definitive surgical resection of primary tumor

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

DRUG: 5-fluorouracil and irinotecan

FOLFIRI.3 given every 14 days x 4 cycles

RADIATION: Preoperative chemoradiation

Pre-operative chemoradiation to 40 Gy in 20 fractions

PROCEDURE: Definitive resection

Definitive surgical resection of primary tumor

Primary Outcome Measures	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	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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Peter Kebbekus, MD, PhD, Essentia Health Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

Patients

Caregivers

Clinical Trial Record