A Phase II Study to Assess the Efficacy and Safety of Preoperative Chemo With Radiation Therapy for Patients With Borderline Unresectable Adenocarcinoma of the Pancreas
Condition: Pancreatic Cancer
MeSH terms: Adenocarcinoma
Intervention: Gemcitabine; Radiation therapy; pancreaticoduodenectomy
Intervention description: The course of preoperative treatment in this study will consist of an alternating combination of 6mg/M² of Gemcitabine for 24 hours and 7.0 Gy (radiation) of radiation therapy. The subject will undergo one of these therapies alternating daily for a total of 10 days then the subject will be allowed to rest for 4 weeks before undergoing restaging and surgery. After surgery, the subject will then undergo the conventional chemotherapy regimen consisting of 6 cycles (1 cycle = 28 days) of 1000mg/M² of Gemcitabine over a 30 minute infusion rate.; The course of preoperative treatment in this study will consist of an alternating combination of 6mg/M² of Gemcitabine for 24 hours and 7.0 Gy (radiation) of radiation therapy. The subject will undergo one of these therapies alternating daily for a total of 10 days then the subject will be allowed to rest for 4 weeks before undergoing restaging and surgery. After surgery, the subject will then undergo the conventional chemotherapy regimen consisting of 6 cycles (1 cycle = 28 days) of 1000mg/M² of Gemcitabine over a 30 minute infusion rate.; Surgery will be planned 28 days (+/- 3 days) after the last dose of chemotherapy. The liver and pancreas will be examined by palpation and inspection. In the absence of metastases, tumor mobilization and surgical resection will be performed with standard surgical technique.
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this phase II clinical trial study is to assess the resection rate among
      subjects who have been initially diagnosed with unresectable or borderline resectable
      pancreatic adenocarcinoma. This will be done by providing preoperative treatment that will
      include alternating cycles of chemotherapy and radiotherapy treatment. In addition, this
      clinical trial will assess the safety of preoperative chemotherapy with radiation therapy for
      subjects with unresectable or borderline resectable adenocarcinoma of the pancreatic head,
      assess margin-negative resection rates, disease-free survival, assess overall survival rates,
      and determine patterns of local and distant recurrence.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Ages 18 years and above. There will be no upper age restriction.

          2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. (See Appendix A
             -ECOG Performance Status Scale).

          3. Cytologic or histologic proof of adenocarcinoma of pancreas.

          4. Adequate renal, and bone marrow function:

               1. Leukocytes >= 3,000/uL (upper limit)

               2. Absolute neutrophil count >= 1,500/uL (upper limit)

               3. Platelets >= 100,000/Ul

               4. Serum creatinine <= 2.0 mg/dL

          5. Hepatic function (endoscopic or percutaneous drainage as needed)

             a. Aspartate aminotransferase (AST)-(SGOT)/Alanine aminotransferase (ALT) (SGPT) <= 5
             X institutional ULN (upper limit of normal)

          6. Borderline resectable pancreatic cancer:

               1. Short segment hepatic artery abutment (< 180° involvement)

               2. Tumor abutment (<180° ) of superior mesenteric artery

               3. Superior mesenteric/portal vein involvement beyond that of a simple resection and
                  reconstruction

               4. Pancreatitis that obscures the determination of vessel involvement and may
                  preclude an otherwise curative operation

          7. Unresectable pancreatic cancer:

               1. Tumors that encase (> 180° involvement) single or multiple arteries and veins
                  (celiac axis, superior mesenteric artery, superior mesenteric/portal vein,
                  hepatic artery)

               2. Occlusion of superior mesenteric/portal vein

        Exclusion Criteria:

          1. Infections such as cholangitis, pneumonia, or wound infections that would preclude
             protocol therapy.

          2. Women with a positive urine or serum pregnancy test are excluded from this study;
             women of childbearing potential (defined as those who have not undergone a
             hysterectomy or who have not been postmenopausal for at least 24 consecutive months)
             must agree to refrain from breast feeding and practice adequate contraception as
             specified in the informed consent. Adequate contraception consists of oral
             contraceptive, implantable contraceptives, injectable contraceptives, a double barrier
             method, or abstinence.

          3. Subjects cannot have known heptic or peritoneal metastases detected by ultrasound
             (US), CT scan, or laparotomy/laparoscopy prior to treatment.

          4. Subjects with unstable angina or New York Heart Association (NYHA) Grade II or greater
             congestive heart failure will be excluded (see Appendix B).

          5. Known presence of central nervous system or brain metastases

          6. Subjects with prior radiotherapy to the upper abdomen or liver will be excluded.

          7. Subjects will be excluded if deemed unable to comply with study and/or follow-up
             procedures.

          8. Subjects with a known hypersensitivity to Gemzar are excluded.

          9. Multiple positive lymph nodes, which will make the radiotherapy treatment volume too
             large. Peripancreatic involved nodes can be included in the radiotherapy treatment
             volume if the field of involved nodes is less than 7.5cm.