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Induction Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma A Prospective Evaluation in Patients With Locally Advanced Pancreas Cancer

Phase 2
18 Years
Open (Enrolling)
Pancreatic Cancer

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Trial Information

Induction Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma A Prospective Evaluation in Patients With Locally Advanced Pancreas Cancer

All subjects will have a baseline CT or FDG-PET/CT prior to initiation of therapy. This will
be done at the Hillman or in Radiation Oncology. Enrolled patients will undergo appropriate
lab work and staging as described

1. Albumin, alkaline phosphatase, glucose, electrolytes

2. Ca 19-9 and CEA

3. Due to an interaction of capecitabine and oral coumadin-derivative anticoagulants and
risk of bleeding/thrombotic events, if a patient is on coumadin, frequent monitoring of
INR and dose adjustments of anticoagulants must be exercised during protocol treatment.
Alternatively, low molecular weight heparin may be substituted for oral anticoagulants
Chemotherapy will be initiated consisting of gemcitabine 1000mg/m2 IV on day 1 and 8 of
a 21 day cycle. Dosage for gemcitabine is described below using the Body surface area

BSA will be calculated from body weight in kg, recorded prior to every gemcitabine dosing,
and height in cm, recorded at baseline.

Premedication for Gemcitabine

A standard, FDA-approved antiemetic medication will be administered to study participants at
the discretion of the treating oncologist (investigator) one-half hour prior to the
gemcitabine infusion. Examples of standard antiemetics include ondansetron (Zofran),
granisetron (Kytril), dolasetron (Anzemet), compazine, and dexamethasone. The dosage and
route of administration will be determined by the treating oncologist based upon the given
clinical scenario.

In addition, capecitabine 650mg/m2 PO will be taken twice daily on days 1-14 of a 3 week
cycle. Four cycles total (12 weeks) of chemotherapy will be given. Dosage for capecitabine
is described below using the Body surface area (BSA).

BSA will be calculated from body weight in kg, recorded prior to every capecitabine dosing,
and height in cm, recorded at baseline.

Capecitabine (Xeloda; F. Hoffmann-La Roche AG, Basel, Switzerland) is supplied as film-coated
tablets in two dose strengths (150 and 500 mg); the closest practical dose (by rounding up
or down) calculated on body-surface area based on a combination of tablets is taken within
30 minutes after the end of a meal.

Patients will be assessed during chemotherapy with appropriate dose modifications made based
on toxicity. Following the completion of chemotherapy, a new FDG-PET/CT or CT will be
obtained to assess response and plan for SBRT. For those patients with SD, PR, or CR, SBRT
will be planned and delivered.

Fidiucial placement In addition, all patients will have fiducial markers placed for
localization at time of SBRT. Three to five soft-tissue fiducials (markers) will be placed
in and/or around the tumor, at least 1cm apart. Oftentimes, these are placed at the time of
endoscopic ultrasound and biopsy for diagnosis. If that is not the case, patients will be
scheduled for a repeat EUS and have the markers placed prior to CT or FDG-PET/CT simulation.
Alternatively, fiducials may be placed at the time of staging laparoscopy.

Stereotactic Body Radiotherapy Planning SBRT will be done in Shadyside Radiation Oncology.

An SBRT plan will be created based on the disease contoured on the CT and PET. The plan will
be to deliver fractionated SBRT to the isodose line best encompassing the PTV:

12 Gy x 3 fractions (36 Gy total)

Careful evaluation of the each plan will be conducted by the radiosurgical team to ensure
that normal tissues and critical structures tolerances are maintained.

The maximum dose (in Gy) within the treatment volume (MD), prescriptions dose (PD), and the
ratio of MD/PD (as a measure of heterogeneity within the target volume), prescription
isodose volume (PIV in mm3), tumor volume (TV in mm3), and the ratio of PIV/TV (as a measure
of dose conformity of the treatment relative to the target) will be recorded.

Quality of Life Assessment Quality of life assessment using the Functional Assessment of
Cancer Therapy - General (FACT-G) tool, which is a validated tool, will be administered to
all subjects prior to treatment and at each follow-up visit.

For patients with potentially resectable tumors, they will be assessed 10 - 12 weeks after
SBRT by a multidisciplinary team including two expert pancreas surgeons and by FDG-PET/CT or
CT scan. If deemed appropriate, patients with an adequate response will be taken for
surgical resection. This will be performed as standard care.

Time frames for chemotherapy and SBRT for 4 cycles of gemcitabine and capecitabine. The SBRT
will not start until twelve weeks after the chemotherapy stops and will last approximately
one week. Each cycle of gemcitabine and capecitabine is three weeks. Upon completion of
treatment patients will be followed for survival for 24 months. They will be in the study
for approximately two years give or take a few months.

Interim medical history and physical examination 4 - 6 weeks after SBRT.

Serum chemistry and electrolytes to include BUN, creatinine, sodium, potassium, bicarbonate,
chloride, calcium, magnesium, glucose, total bilirubin, AST, ALT, alkaline phosphatase prior
to chemotherapy treatments, 4 -6 weeks post-SBRT treatment, and then at follow-up as
clinically indicated

Hematologic studies to include CBC with differential and platelet count weekly during
chemotherapy sessions and then repeated 4-6 weeks post-SBRT treatment and then at follow-up
as clinically indicated

CT or FDG-PET/CT scans (for consistency procedure done at screening/planning will continue
in follow-up) will be obtained at 10-12 weeks post-treatment and will be reviewed for
evidence of response. Subjects who demonstrate no evidence of distant metastases and meet
RECIST criteria of partial response, complete response, or stable disease will be offered
surgical exploration and attempted curative resection. Subjects demonstrating unresectable
disease or progression of disease will be started on systemic chemotherapy at the discretion
of the treating medical oncologist.

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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Local progression-free survival (LPFS) achieved in subjects with locally-advanced, potentially resectable pancreatic adenocarcinoma treated with SBRT and gemcitabine/capecitabine chemotherapy

Outcome Description:

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.

Outcome Time Frame:

24 months

Safety Issue:


Principal Investigator

Dwight E Heron, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UPMC Shadyside


United States: Institutional Review Board

Study ID:




Start Date:

July 2011

Completion Date:

June 2015

Related Keywords:

  • Pancreatic Cancer
  • Pancreas
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Pancreatic Neoplasms



UPMC Cancer CentersPittsburgh, Pennsylvania  15232