Chemoradiation And Radiosurgery Boost In Treating Patients With Locally Advance Pancreatic Cancer That May Or May Not Be Removed By Surgery

Study Overview

Chemoradiation and Radiosurgery Boost in Treating Patients With Locally Advance Pancreatic Cancer That May or May Not be Removed by Surgery

This phase I trial studies the side effects and best dose of radiosurgery boost following chemoradiation in treating patients with locally advanced pancreatic cancer that may or may not be removed by surgery. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue. Giving chemotherapy and radiation therapy together with radiosurgery may kill more tumor cells and allow doctors to save the part of the body where the cancer started

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) of a radiosurgery boost added to hypofractionated chemoradiation in patients with borderline resectable or unresectable pancreatic cancer. SECONDARY OBJECTIVES: I. To determine the effect of a radiosurgery boost added to hypofractionated chemoradiation on surgical morbidity (specifically, healing of the surgical anastomoses and abdominal wounds and late hemorrhage from blood vessels in the field) in patients with advanced borderline resectable (BLR) or unresectable pancreatic cancer. II. To evaluate the utility of diffusion-weighted magnetic resonance imaging (MRI) as an assessment of treatment response after chemoradiation followed by radiosurgery. III. To determine the feasibility of collecting tissue for immunohistochemistry (IHC) analysis via endoscopic ultrasound or computed tomography (CT)-guided fine needle aspiration. IV. To utilize pathologic response rates in dose escalated regions, hypofractionated regions, and the dose gradient region in between to better characterize the radiobiologic response of pancreatic cancer to radiation dose escalation. OUTLINE: This is a dose-escalation study of radiosurgery. Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes once weekly and undergo hyperfractionated intensity-modulated radiation therapy (IMRT) 5 days a week in weeks 1-3. Patients then undergo a single fraction of radiosurgery boost in week 5 and then receive gemcitabine hydrochloride IV over 30 minutes once weekly in weeks 6-8. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 2 years, and then annually thereafter.

Acinar Cell Adenocarcinoma of the Pancreas
Duct Cell Adenocarcinoma of the Pancreas
Stage IIB Pancreatic Cancer
Stage III Pancreatic Cancer

DRUG: gemcitabine hydrochloride
RADIATION: hyperfractionated radiation therapy
RADIATION: intensity-modulated radiation therapy
RADIATION: radiosurgery
PROCEDURE: diffusion-weighted magnetic resonance imaging

12-046
NCI-2012-02729 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))

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 2012-11-29	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2019-07-26
First Submitted that Met QC Criteria 2012-11-29	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2019-07-29
First Posted (ACTUAL) 2012-12-03	Results First Posted N/A	Last Verified 2019-07

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:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (chemoradiation and radiosurgery) Patients receive gemcitabine hydrochloride IV over 30 minutes once weekly and undergo hyperfractionated IMRT 5 days a week in weeks 1-3. Patients then undergo a single fraction of radiosurgery boost in week 5 and then receive gemcitabine hydrochloride IV	DRUG: gemcitabine hydrochloride Given IV RADIATION: hyperfractionated radiation therapy Undergo hyperfractionated IMRT RADIATION: intensity-modulated radiation therapy Undergo hyperfractionated IMRT RADIATION: radiosurgery Undergo radiosurgery boost PROCEDURE: diffusion-weighted magnetic resonance imaging Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (chemoradiation and radiosurgery)

Patients receive gemcitabine hydrochloride IV over 30 minutes once weekly and undergo hyperfractionated IMRT 5 days a week in weeks 1-3. Patients then undergo a single fraction of radiosurgery boost in week 5 and then receive gemcitabine hydrochloride IV

DRUG: gemcitabine hydrochloride

Given IV

RADIATION: hyperfractionated radiation therapy

Undergo hyperfractionated IMRT

RADIATION: intensity-modulated radiation therapy

Undergo hyperfractionated IMRT

RADIATION: radiosurgery

Undergo radiosurgery boost

PROCEDURE: diffusion-weighted magnetic resonance imaging

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
MTD defined as the dose level in which 1 out of 6 patients observes dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0		Week 5

Secondary Outcome Measures	Measure Description	Time Frame

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:

Patients must have histologically or cytologically-confirmed pancreatic adenocarcinoma
For the initial dose escalation study, patients must have locally advanced / unresectable pancreatic cancer; these are defined as follows:

No distant metastases
Hepatic artery encasement
Superior mesenteric artery (SMA) encasement > 180 degrees
Any celiac axis abutment
Unreconstructable superior mesenteric vein (SMV)/portal occlusion
Aortic invasion or encasement
Metastases to lymph nodes beyond the field of resection
For the expansion phase, patients must have borderline resectable or locally advanced / unresectable pancreatic cancer; these are defined as follows:

No distant metastases
At least 45 degree abutment of the hepatic artery or SMA
Any celiac axis abutment
Near complete occlusion of the SMV or portal vein
Unreconstructable or reconstructible SMV/portal occlusion
Aortic invasion or encasement
Metastases to lymph nodes beyond the field of resection
Patients must have evaluable disease
Women of childbearing potential must be non-pregnant (negative pregnancy test within 72 hours prior to radiation simulation, postmenopausal woman must have been amenorrheic for at least 12 months to be considered of non-childbearing potential) and nonlactating, and men and women must be willing to exercise an effective form of birth control (abstinence/contraception) while on study and for 3 months after therapy completed
Eastern Cooperative Oncology Group (ECOG) performance status determined to be between 0 and 1
Absolute neutrophil count (ANC) >= 1,500/ul
Platelets (PLT) >= 100,000/ul
Subjects must sign a written informed consent and Health Insurance Portability and Accountability Act (HIPAA) consent prior to performance of study-specific procedures or assessments and must be willing to comply with treatment and follow up
Bilirubin less then 1.5 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x ULN
Serum creatinine < 1.5 x ULN

Patients who have had any prior therapy for pancreatic cancer
Concurrent chemotherapy or biologic therapy
A history of ataxia telangiectasia or other documented history of radiation hypersensitivity
Scleroderma or active connective tissue disease
Active inflammatory bowel disease
Serious, active infections requiring treatment with IV antibiotics
Uncontrolled intercurrent illness including, but not limited to, psychiatric illness/social situations that would limit compliance with study requirements

Collaborators and Investigators

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

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Joshua Meyer, Fox Chase 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

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Clinical Trial Record