A Phase II Randomized Study of Induction Chemotherapy Followed by Concurrent Chemo-radiotherapy in Locally Advanced Pancreatic Cancer
Patients should be randomized to two study arms stratified by resectability status
(borderline resectable and unresectable) after enrollment. Eligible patients will be
randomly assigned on a 1:1 basis to either of two study groups, using a central
randomization procedure with stratification according to NCCN criteria of resectability.
After randomization, induction chemotherapy (ICT) will be administered for 3 cycles (3
months). Patients who have radiological evidence of distant dissemination will be shifted to
salvage chemotherapy. Patients who have responsive, stable disease as well as those with
localized progressive disease after ICT will receive concurrent chemoradiotherapy (CCRT) 3-4
weeks after the last dose of ICT. Surgical evaluation will be performed 4-6 weeks after the
completion of CCRT. Patients who have respectable disease will undergo surgical resection.
Postoperative adjuvant chemotherapy for 3 cycles (3 months) will be given for those who are
considered to have curative resection. Patients who still have unresectable disease or
non-curative resection will receive systemic chemotherapy till disease progression or
For Arm 1, ICT with FOLFIRINOX ( oxaliplatin 85mg/m2 for 2 hr, irinotecan 180mg/m2 for 90
min and 5FU 3000mg/m2 + LV 150mg/m2 continuous infusion 48 hr) will be administered
biweekly. For Arm 2, ICT with GOFL ( 800mg/m2 gemcitabine at a fixed rate of 10mg/m2/min
followed by a 2-hour oxaliplatin 85mg/m2 and then a 48-hour 3000mg/m2 5-FU and 150 mg/m2
leucovorin on day 1 and 15 every 28 days/cycle) will be given biweekly.
After three 3 cycles of ICT, patients without distant metastasis will be given CCRT with
5-FU 450mg/m2 in Arm 1, gemcitabine 400mg/m2 in Arm 2, 2 hrs before RT on
day1,8,15,22,29,36. Radiation will be given 180cGy per day, 5 days a week for 28 fractions
to totally 5040cGy.
If complete surgical resection is feasible, optimal surgery will be performed 4-6 weeks
after CCRT. If complete surgical resection is impossible, biopsy with or without bypass
surgery may be performed. Patients who have curative surgical resection will receive
additional 6 cycles ( 6 months) of adjuvant chemotherapy ( Arm1, FOLFIRINOX, Arm 2, GOFL)
within 4 weeks after surgery and then followed up until tumor progression. Patients who are
not feasible for curative resection, will receive continued chemotherapy (Arm1, FOLFIRINOX;
Arm2, GOFL) 3-4 weeks after CCRT complete. The regimen will continue till disease
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
the response rate, disease control rate, overall survival, and patients' quality of life.
This is a randomized phase II trial of ICT followed by CCRT with radiotherapy in LAPC. The efficacy will be primarily measured by progression free survival (PFS) as defined in Section 8.5.Other measurements include the response rate, disease control rate, overall survival, and patients' quality of life as described in Section 8.We anticipate that the attrition rate is about 10%, hence, roughly 86 patients will be recruited , we anticipate that the recruitment will be completed in 4.5 years.
Yen-Shen Shen, M.D.
National Cheng-Kung University Hospital
Taiwan: Department of Health