Systemic Therapy and Chemoradiation in Advanced Localised Pancreatic Cancer - 2 (SCALOP-2)

This is an interventional treatment trial for Pancreatic Neoplasms (Locally Advanced Non-metastatic) focused on measuring chemoradiotherapy, nelfinavir, abraxane, gemcitabine, radiotherapy, capecitabine Read More

Inclusion criteria:

1. 1. Aged 18 years or over
2. Histologically or cytologically proven carcinoma of the pancreas

3. Locally advanced, non-metastatic inoperable disease as per NCCN criteria (APPENDIX 2). The following types of interventions are allowed:

   1. Palliative bypass procedure
   2. Common bile duct stenting
4. Primary pancreatic lesion 6 cm or less in diameter (taken from scan results)
5. WHO PS 0-1 (APPENDIX 1)
6. Adequate haematological function: neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/L and haemoglobin ≥100g/L

7. Adequate liver function tests:

   1. Serum bilirubin ≤1.5 x ULN. In participants who have had a recent biliary drain and whose bilirubin is improving, a value of ≤3 x ULN is acceptable, however treatment should not start unless Bilirubin is ≤1.5 x ULN.
   2. AST and/or ALT ≤ 3 x ULN.
8. Adequate renal function (GFR ≥ 50ml/min (Cockcroft & Gault - APPENDIX 3))
9. Written informed consent obtained
10. Women of child-bearing potential must have negative serum or urine pregnancy test within 14 days prior to registration, must agree to use a highly effective contraception method during GEMABX treatment and for 30 days after last administration of GEMABX and to use an acceptable contraception method during chemoradiotherapy and for 6 months after completion of all treatment.
11. Male patients must be surgically sterile or must agree to use a condom during GEMABX treatment and for 90 days after last administration of GEMABX, and to use a condom during chemoradiotherapy and for three months after completion of chemoradiotherapy.

Exclusion criteria:

1. Primary resectable cancer of the pancreas.
2. Distant metastases
3. Pregnant or breast-feeding patients.
4. Any evidence of severe uncontrolled systemic diseases including uncontrolled coronary artery disease, myocardial infarction or stroke within the last 6 months, any major systemic or psychiatric co-morbidities or any other considerations that the PI judges might impact on patient safety or protocol compliance and achievement of the study aims.

5. Previous malignancies in the preceding 3 years except for:

   1. In situ cancer of the uterine cervix
   2. Adequately treated basal cell skin carcinoma
   3. Adequately treated early stage non-pancreatic malignancy in complete remission for at least 3 years
6. Renal abnormalities including adult polycystic kidney disease or hydronephrosis or ipsilateral single kidney (i.e. functioning right kidney for head tumours; left kidney for tail tumours) that may preclude upper abdominal radiotherapy without damaging functional kidneys.
7. Previous RT to upper abdomen
8. Recurrent cancer following definitive pancreatic surgery
9. Lymphoma or neuroendocrine tumours of the pancreas
10. Known haemophilia A and B, chronic hepatitis type B or C.
11. Other experimental treatment 6 weeks or less prior to registration into this study (including chemothera¬py and immunotherapy).
12. Known hypersensitivity to any of the IMPs or any of their excipients.
13. Known dihydropyrimidine dehydrogenase (DPD) deficiency
14. Known galactose intolerance, Lapp-lactose deficiency or glucose-galactose malabsorption
15. History of severe unexpected reaction to fluoropyrimidine therapies

16. If the following concomitant medications cannot be discontinued temporarily during the CRT phase then the patients cannot enter the trial:

    1. Sorivudine and analogues e.g. brivudine
    2. Methotrexate.
    3. Allopurinol and dipyridamole
17. Known HIV positive disease (but routine screening for HIV is not required)