High or Standard Intensity Radiation Therapy After Gemcitabine Hydrochloride and Nab-paclitaxel in Treating Patients With Pancreatic Cancer That Cannot Be Removed by Surgery
Condition: Pancreatic Adenocarcinoma; Stage III Pancreatic Cancer
MeSH terms: Pancreatic Neoplasms
Intervention: low intensity radiation therapy; Capecitabine; Gemcitabine; high intensity radiation therapy; nab-Paclitaxel
Intervention description: 50.4 Gy in 28 1.8 Gy fractions (IMRT or 3D-CRT), 5 days/week, starting 3-5 weeks after the last dose of induction chemotherapy; 825 mg/m2 PO twice daily, 5 days/week, beginning on the first day of radiation therapy and ending on the last day of radiation therapy.; 1000 mg/m2 weekly as a 30 minute infusion after nab-Paclitaxel, three weeks on and 1 week off [1 cycle = 4 weeks]; 63 Gy intensity-modulated radiation therapy (IMRT) in 28 2.25 Gy fractions, 5 days/week, starts 3-5 weeks after the last dose of induction chemotherapy; 125 mg/m2 weekly as a 30-40 minute infusion, three weeks on and 1 week [1 cycle = 4 weeks]
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel; Gemcitabine; Capecitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: SMAD4; IMRT; gemcitabine; high-dose radiotherapy

Summary:

      This randomized phase II trial studies how well high or standard intensity radiochemotherapy
      after gemcitabine hydrochloride and paclitaxel albumin-stabilized nanoparticle formulation
      (nab-paclitaxel) work compared with gemcitabine hydrochloride and nab-paclitaxel alone in
      treating patients with pancreatic cancer that cannot be removed by surgery. Drugs used in
      chemotherapy, such as gemcitabine hydrochloride and nab-paclitaxel, work in different ways to
      stop the growth of tumor cells, either by killing the cells, by stopping them from dividing
      or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor
      cells. Drugs, such as capecitabine, may make tumor cells more sensitive to radiation therapy.
      Giving radiation therapy in different ways and adding chemotherapy may kill more tumor cells.
      It is not yet known whether high intensity radiochemotherapy after gemcitabine hydrochloride
      and nab-paclitaxel is more effective than standard intensity radiochemotherapy after
      gemcitabine hydrochloride and nab-paclitaxel or gemcitabine hydrochloride and nab-paclitaxel
      alone in treating pancreatic cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically or cytologically proven diagnosis of adenocarcinoma of the pancreas
             prior to registration

          2. Tumor diameter ≤ 7 cm

          3. Unresectable by radiographic criteria (pancreas protocol CT or MRI) or exploration
             within 30 days prior to registration.

          4. A cell block or core biopsy must be submitted for central review and analysis of SMAD4
             status as soon as possible following step 1 registration.

          5. No distant metastases, based upon the following minimum diagnostic workup:

               -  History/physical examination within 30 days prior to registration

               -  Whole body fluorodeoxyglucose-positron emission tomography/computerized
                  tomography (FDG-PET/CT) within 30 days prior to registration NOTE: If whole-body
                  FDG-PET/CT is not performed, CT of the chest and CT (or MRI) of abdomen and
                  pelvis must be obtained (imaging of abdomen and pelvis need not be repeated if
                  already included in pancreas protocol study)

          6. Zubrod Performance Status 0-1 within 30 days prior to registration

          7. Age ≥ 18;

          8. Complete blood count (CBC)/differential obtained within 14 days prior to step 1
             registration, with adequate bone marrow function defined as follows:

               -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

               -  Platelets ≥ 100,000 cells/mm3

               -  Hemoglobin ≥ 8.0 g/dl (NOTE: The use of transfusion or other intervention to
                  achieve Hgb ≥ 8.0 g/dl is acceptable)

          9. Additional laboratory studies within 14 days prior to registration:

               -  carbohydrate antigen 19-9 (CA19-9); NOTE: in the event that a stent has been
                  placed and biliary obstruction has been relieved, the CA19-9 should be drawn post
                  stent placement

               -  Creatinine < 2 mg/dl; Glomerular filtration rate (GFR) > 50 mL/min (Cockroft and
                  Gault formula)

               -  Bilirubin < 1.5 x ULN

               -  Alanine aminotransferase (ALT) and aminotransferase (AST) ≤ 2.5 x ULN

               -  Activated partial thromboplastin time (aPTT), prothrombin time (PT) ≤1.2 x upper
                  limit of normal (ULN)

         10. Patient must provide study specific informed consent prior to study entry

         11. Women of childbearing potential and male participants must practice adequate
             contraception during protocol treatment and for at least 6 months following treatment

         12. For females of child-bearing potential, negative serum pregnancy test within 30 days
             prior to registration

        Exclusion Criteria:

          1. More than one primary lesion

          2. Prior invasive malignancy (unless disease free for a minimum of 1095 days [3 years]);
             Non-melanomatous skin cancer and previous early prostate cancer that had a non-rising
             prostate-specific antigen (PSA) are eligible

          3. Prior systemic anti-cancer therapy for pancreatic cancer; note that prior chemotherapy
             for a different cancer is allowable

          4. Prior radiation therapy to the abdomen that would result in overlap of radiation
             therapy fields

          5. Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  the last 6 months

               -  Transmural myocardial infarction within the last 6 months

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration

               -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy within 30 days before
                  registration

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
                  note, however, that laboratory tests for liver function and coagulation
                  parameters are not required for entry into this protocol

               -  Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease
                  Control (CDC) definition; note, however, that HIV testing is not required for
                  entry into this protocol. The need to exclude patients with AIDS from this
                  protocol is necessary because the treatments involved in this protocol may be
                  significantly immunosuppressive. Protocol-specific requirements may also exclude
                  immuno-compromised patients

          6. Pregnancy or women of childbearing potential, women who cannot discontinue
             breastfeeding and men who are sexually active and not willing/able to use medically
             acceptable forms of contraception; this exclusion is necessary because the treatment
             involved in this study may be significantly teratogenic

          7. Prior allergic reaction to the study drug(s) involved in this protocol

          8. Pre-existing Grade 2 or greater neuropathy

          9. Distant metastases