Randomized Phase II-III Trial of Peri- or Post-Operative Chemotherapy in Resectable Pancreatic Adenocarcinoma
- To assess the proportion of patients who are event-free (defined as disease
progression, local recurrence, distant metastasis, new tumor, or death) at 1 year after
neoadjuvant therapy comprising gemcitabine hydrochloride with cisplatin, epirubicin
hydrochloride, and capecitabine (PEXG), and adjuvant chemotherapy comprising
gemcitabine hydrochloride or PEXG regimen in patients with resectable stage I or II
adenocarcinoma of the pancreas. (phase II)
- To assess whether the best experimental regimen, which will be selected on the basis of
the phase II part of the trial, is able to improve overall survival when compared to
standard adjuvant gemcitabine in these patients. (phase III)
- To assess radiological, biochemical, and pathological response rate (neoadjuvant arm
only) in these patients.
- To assess surgical resection rate, surgical mortality and morbidity, and proportion of
patients with negative surgical margins.
- To assess lymph node status in these patients.
- To determine tolerability of these regimens in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to center. Patients
are randomized to 1 of 3 treatment arms.
- Arm I (adjuvant gemcitabine hydrochloride) : Patients receive gemcitabine hydrochloride
IV over 1 hour on days 1, 8, and 15. Courses repeat every 28 days for 6 months in the
absence of disease progression or unacceptable toxicity.
- Arm II (adjuvant cisplatin, epirubicin hydrochloride, gemcitabine hydrochloride, and
capecitabine [PEXG regimen]): Patients receive cisplatin IV over 1 hour on days 1-5,
epirubicin hydrochloride IV on days 1 and 8, gemcitabine hydrochloride IV over 1 hour
on days 1 and 8, and oral capecitabine on days 1-14. Treatment repeats every 14 days
for 6 months in the absence of disease progression or unacceptable toxicity.
- Arm III (neoadjuvant and adjuvant PEXG regimen): Patients receive neoadjuvant cisplatin
IV over 1 hour on days 1-5, epirubicin hydrochloride IV on days 1 and 8, gemcitabine
hydrochloride IV over 1 hour on days 1 and 8, and oral capecitabine on days 1-14.
Treatment repeats every 14 days for up to 3 months. Patients then undergo surgery for
pancreatic cancer followed by adjuvant (within 2 months of surgery) PEXG given as in
neoadjuvant therapy. Treatment with adjuvant PEXG repeats every 14 days for 3 months in
the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year,
every 4 months for 2 years, and then every 6 months thereafter.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Event-free survival at 1 year (phase II)
every 3 months
Michele Reni, MD
Istituto Scientifico H. San Raffaele
Italy: Ministry of Health