This phase III trial studies how well carbon ion radiation therapy works compared to conventional photon radiation therapy when giving together with chemotherapy in treating patients with pancreatic cancer that has spread from its original site of growth to nearby tissues or lymph nodes (locally advanced) and cannot be removed by surgery (unresectable). Carbon ion radiation therapy uses charged carbon particles to kill tumor cells and shrink tumors. Conventional photon radiation therapy, such as intensity-modulated radiation therapy is a type of 3-dimensional radiation therapy that uses computer-generated images to show the size and shape of the tumor. This type of radiation therapy reduces the damage to healthy tissue near the tumor. Drugs used in chemotherapy, such as gemcitabine, nab-paclitaxel, capecitabine, fluorouracil, irinotecan, leucovorin and oxaliplatin 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. Given carbon ion radiation therapy with chemotherapy may kill more tumor cells in patients with pancreatic cancer compared to conventional photon radiation therapy and chemotherapy.
Additional locations may be listed on ClinicalTrials.gov for NCT03536182.
See trial information on ClinicalTrials.gov for a list of participating sites.
PRIMARY OBJECTIVE:
I. To compare the efficacy of carbon ion-based chemoradiotherapy with x-ray-based chemoradiotherapy for the treatment of locally advanced pancreatic adenocarcinoma by comparison of overall survival at 2 years following treatment.
SECONDARY OBJECTIVES:
I. To compare progression-free survival between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.
II. To compare patterns-of-failure between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.
III. To compare quality-of-life and toxicity outcomes between x-ray-based and carbon-ion-based chemoradiotherapy treatment courses for locally advanced pancreatic adenocarcinoma.
EXPLORATORY OBJECTIVE:
I. To compare quality-adjusted survival time between x-ray-based and carbon-ion-based chemoradiotherapy.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Within 6 weeks of the conclusion of the last cycle neoadjuvant chemotherapy, patients undergo carbon ion radiation therapy daily 4 days per week for 3 weeks. Patients also receive concurrent gemcitabine intravenously (IV) over 1 hour during weeks 1-3 of radiotherapy. Starting within 6 weeks of completing radiation therapy, patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30 minutes weekly for 3 weeks or FOLFIRINOX. Treatment repeats every 4 weeks for up to 2 (if receiving neoadjuvant chemotherapy) or 4 (if no prior neoadjuvant chemotherapy) cycles in the absence disease progression or unacceptable toxicity. In countries without access to these drugs, gemcitabine alone is acceptable.
ARM B: Within 6 weeks of the conclusion of the last cycle neoadjuvant chemotherapy, patients undergo intensity-modulated radiation therapy 5 days per weeks for 5 weeks. Patients also receive concurrent gemcitabine IV over 1 hour or capecitabine orally (PO) twice daily (BID) during weeks 1-5 of radiotherapy. Starting within 6 weeks of completing radiation therapy, patients receive nab-paclitaxel IV over 30-40 minutes and gemcitabine IV over 30 minutes weekly for 3 weeks or FOLFIRINOX. Treatment repeats every 4 weeks for up to 2 (if receiving neoadjuvant chemotherapy) or 4 (if no prior neoadjuvant chemotherapy) cycles in the absence disease progression or unacceptable toxicity. In countries without access to these drugs, gemcitabine alone is acceptable.
FOLFIRINOX: Patients receive oxaliplatin IV , leucovorin IV, and irinotecan IV on days 1 and 15, and fluorouracil IV over 46 hours on days 1-3 and 15-17.
After completion of study treatment, patients are followed up every 3 months.
Lead OrganizationUT Southwestern/Simmons Cancer Center-Dallas
Principal InvestigatorDavid Jonathan Sher