Short Course Radiation Therapy With Proton Beam Capecitabine and Hydroxychloroquine for Resectable Pancreatic Cancer

• Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine the progression-free survival of the addition of hydroxychloroquine to preoperative short course, proton-based chemoradiation therapy and adjuvant gemcitabine chemotherapy
  
  

• Pathologic response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine the complete pathologic response rate of preoperative capecitabine combined with hydroxychloroquine and proton beam radiation therapy in patients undergoing pancreaticduodenectomy
  
  
• Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine overall survival in patients treated with preoperative capecitabine + hydroxychloroquine and proton beam radiation therapy
  
  
• Toxicity/Adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To determine the toxicity of capecitabine + hydroxychloroquine and proton beam radiation therapy in patients with pancreatic cancer via analysis of frequency and grades of reported toxicities and adverse events, such as GI and heamtologic toxicities, occuring in study participapants
  
  
• Surgical morbidity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
  To determine the surgical morbidity in patients undergoing pancreaticduodenectomy who received preoperative capecitabine + hydroxychloroquine and external beam radiation therapy
  
  
• Post-operative Mortality [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
  To determine 30-day post-operative mortality after pancreaticoduodenectomy in patients who receive preoperative capecitabine and external beam radiation therapy
  
  
• Biomarkers [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To explore biiomarkers of autophagy with hydroxychloroquine therapy and explore correlation with progression-free survival
  
  
• Pathologic downstaging [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine pathlogic downstaging of hydroxychloroquine-based short course chemoradiation compared to a previous cohort (treated in prior study of neoadjuvant capecitabine + proton therapy)
  
  
• Local control [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  To determine local tumor control at 2 years post treatment in study participants
  
  

Subjects will be treated in cycles of 28 days. Hydroxychloroquine will be taken orally, daily until the day before surgery and will resume after surgery until study end.

Capecitabine will be taken orally, daily. Proton radiation treatment will start on Week 2 and will be delivered daily (5 days in a row, but not weekends or holidays). Radiation treatment will be give on an outpatient basis at the Francis H. Burr Proton Center at Massachusetts General Hospital.

The following tests will be performed weekly: physical exam, routine blood tests, optional blood tests and an eye exam every 3 months while taking hydroxychloroquine.

Subjects will have surgery (any time between Weeks 5 to 9) and after surgery resume taking hydroxychloroquine. Subjects will have a follow up visit every 3 months which will include: physical exam, routine blood tests, eye exam, and tumor assessment by chest and abdominal-pelvic CT scan or MRI (every 6 months for the first 2 years and yearly for years 3-5).