Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by University of Pittsburgh
Sponsor:
Information provided by (Responsible Party):
Dwight Heron, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01360593
First received: May 24, 2011
Last updated: January 30, 2014
Last verified: January 2014
  Purpose

The current study seeks to further investigate the impact of up-front systemic therapy in combination with fractionated SBRT for potentially resectable, locally-advanced pancreatic adenocarcinoma.


Condition Intervention Phase
Pancreatic Cancer
Drug: Gemcitabine
Drug: Capecitabine
Radiation: Stereotactic Body Radiation Therapy (SBRT)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Induction Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma A Prospective Evaluation in Patients With Locally Advanced Pancreas Cancer

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Local progression-free survival (LPFS) achieved in subjects with locally-advanced, potentially resectable pancreatic adenocarcinoma treated with SBRT and gemcitabine/capecitabine chemotherapy [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    In this study, LPFS is defined as the time from enrollment to first documentation of progressive disease (PD) in the target lesion. Death or development of distant disease is not regarded as an event. For patients that undergo surgical resection, local progression will be defined as disease recurrence detected on follow-up imaging (CT or FDG-PET/CT) that is located within the SBRT target volume.


Secondary Outcome Measures:
  • Objective response rate, time to progression (TTP) and overall survival (OS) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    TTP is defined as the time from enrollment to disease progression. Disease progression will be defined as PD in the target volume, or development of distant disease. OS is defined as the length of time from enrollment to confirmed death from any cause.

  • Number of patients that are able to undergo a margin-negative resection after neoadjuvant therapy [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    All patients that undergo attempted surgical evaluation will have their pathology records reviewed and discussed with the operating surgeon to determine margin status. Margins will be classified as negative, close (1-2.5mm), microscopically positive, and grossly positive.

  • QOL of subjects treated with SBRT for unresectable locally-advanced pancreatic adenocarcinoma [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    QOL evaluation will be administered prior to SBRT, after completion of SBRT, and at each follow-up. The survey will be the FACT-G

  • Measure acute and late toxicities associated with SBRT for locally advanced pancreas cancer [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    All patients will be monitored for potential treatment-related toxicity throughout treatment as detailed in the schema. Toxicity will be graded according to the CTCAE v4. Acute toxicity is defined as toxicity occurring within 3 months of completion of SBRT. Late toxicity is defined as toxicity occurring greater than 3 months after treatment.

  • Role of FDG-PET/CT in the setting of pancreatic cancer [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Ideally, all follow-up FDG-PET/CT scans after chemo will be performed on the same scanner to help limit variability in the SUVs detected by different scanners. For those patients with non-FDG avid tumors, their response to therapy will be assessed by CT scan. The most recent consensus recommendations by the NCI on assessing PET response indicate semi-quantitative SUV (standard uptake value) analysis based on lean body mass and/or body surface area be used in determining 18F-FDG uptake. We will use the EORTC 1999 criteria for defining 18F-FDG response


Estimated Enrollment: 50
Study Start Date: July 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Gem, Xeloda, SBRT Drug: Gemcitabine

Gemcitabine will be administered for 2 weekly doses every 3 weeks commencing 12 weeks prior to stereotactic radiosurgery as follows:

Gemcitabine 1,000 mg/m2 IV over 30 minutes on Day 1, and 8 of 21- day cycle. This will be done for up to 4 cycles.

Other Name: Gemzar
Drug: Capecitabine

Capecitabine will be taken orally twice daily on days 1-14 every 3 weeks for 4 cycles (12 weeks) prior to stereotactic radiosurgery as follows:

Capecitabine 650 mg/m2 twice daily for days 1-14 every 3 weeks for up to 4 cycles.

Other Name: Xeloda
Radiation: Stereotactic Body Radiation Therapy (SBRT)

Fractionated SBRT will be delivered to patients that have stable disease, partial response, or complete response after chemo in the following manner:

12 Gy x 3 fractions (36 Gy total) This will be given every other day.

Other Names:
  • CyberKnife
  • Trilogy
  • True Beam
  • Radiosurgery
  • SBRT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically proven adenocarcinoma of the pancreas
  • Subjects will be staged according to the 2010 AJCC staging system with pathologic stage T1-4, N0-1 being eligible; and have a primary tumor of the pancreas (i.e., pancreatic head, neck, uncinate process, body/tail
  • Tumor must be deemed to be borderline resectable or locally advanced by radiographic criteria defined by Varadhachary et al.26 Final CT confirmation of surgical staging/eligibility will be by two expert pancreatic surgeons
  • Disease confined to locoregional site confirmed by FDG-PET/CT or CT and diagnostic staging laparoscopy to ensure no occult peritoneal implants
  • Disease must be encompassed in a reasonable SBRT "portal" as defined by the treating radiation oncologist
  • Measurable disease on imaging studies (MRI, CT, FDG-PET/CT or physical exam), including maximum diameter/dimension, must be present for assessment of response
  • Karnofsky performance status > 70 (ECOG 0-1)
  • Age > 18
  • Estimated life expectancy > 12 weeks
  • Patient must have adequate renal function as defined by serum creatinine<1.5mg/dl obtained within 28 days prior to registration
  • Patient must have adequate bone marrow function as defined by absolute neutrophil count>1500/mcl and platelets>100,000/mcl, obtained within 28 days prior to registration
  • Patient must have adequate hepatic function as defined by total bilirubin <1.5 x IULN(institutional upper limit of normal) and either SGOT or SGPT <2.5x IULN, obtained within 28 days prior to registration.
  • Patient must be able to swallow enteral medications. Patient must not require a feeding tube. Patient must not have intractable nausea or vomiting, GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, or uncontrolled inflammatory bowel disease (Chron's, ulcerative colitis).
  • Diabetes must be controlled prior to FDG-PET/CT scanning (blood glucose <200 mg/dL)
  • Ability to provide written informed consent
  • Patient must not have uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, history of myocardial infarction or cerebrovascular accident within 3 months prior to registration, uncontrolled diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Patient must not be pregnant because of the risk of harm to the fetus. Nursing women may participate only if nursing is discontinued, due to the possibility of harm to nursing infants from the treatment regimen. Women/men of reproductive potential must agree to use an effective contraception method.

Exclusion Criteria:

  • Non-adenocarcinomas, adenosquamous carcinomas, islet cell carcinomas, cystadenomas, cystadenocarcinomas, carcinoid tumors, duodenal carcinomas, distal bile duct, and ampullary carcinomas are not eligible.
  • Evidence of distant metastasis on upright chest x-ray (CXR), computed tomography (CT) or other staging studies
  • Subjects with recurrent disease
  • Prior radiation therapy to the upper abdomen or liver
  • Prior chemotherapy
  • Subjects in their reproductive age group should use an effective method of birth control. Subjects who are breast-feeding, or have a positive pregnancy test will be excluded from the study
  • Any co-morbidity or condition of sufficient severity to limit full compliance with the protocol per assessment by the investigator
  • Concurrent serious infection
  • Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ, adequately treated basal cell or squamous cell carcinoma of the skin, and treated low-risk prostate cancer.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01360593

Contacts
Contact: Dwight E Heron, MD 412-623-6720 herond2@upmc.edu
Contact: Karen D Holeva 412-623-1275 holevakd@upmc.edu

Locations
United States, Pennsylvania
UPMC Cancer Centers Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Dwight E Heron, MD    412-623-6720    herond2@upmc.edu   
Contact: Karen D Holeva    412-623-1275    holevakd@upmc.edu   
Sub-Investigator: Steven A Burton, MD         
Sub-Investigator: John Flickinger, MD         
Sub-Investigator: Cihat Ozhasoglu, PhD         
Sub-Investigator: Annette E Quinn, MSN         
Sub-Investigator: Herbert Zeh, MD         
Sub-Investigator: Kenneth Lee, MD         
Sub-Investigator: A. James Moser, MD         
Sub-Investigator: Nathan Bahary, MD         
Sub-Investigator: Barry Lembersky, MD         
Sub-Investigator: Ronald Stoller, MD         
Sub-Investigator: David M Friedland, MD         
Sub-Investigator: James Mountz, MD         
Sub-Investigator: Alyssa Krasinskas, MD         
Sub-Investigator: Hong Wang, PhD         
Sponsors and Collaborators
University of Pittsburgh
Investigators
Principal Investigator: Dwight E Heron, MD UPMC Shadyside
Principal Investigator: Rodney Wegner, MD UPMC Shadyside
  More Information

No publications provided

Responsible Party: Dwight Heron, Vice Chairman of Clinical Affairs, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01360593     History of Changes
Other Study ID Numbers: 08-139
Study First Received: May 24, 2011
Last Updated: January 30, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Pittsburgh:
Pancreas

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Capecitabine
Fluorouracil
Gemcitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on September 30, 2014