Gemcitabine/Capecitabine Followed by SBRT in Pancreatic Adenocarcinoma
Condition: Pancreatic Cancer
MeSH terms: Adenocarcinoma
Intervention: Gemcitabine; Capecitabine; Stereotactic Body Radiation Therapy (SBRT)
Intervention description: 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.; 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.; 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.
Intervention MeSH terms: Gemcitabine; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pancreas

Summary:

      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.
    

Eligibility 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.