Chemotherapy Before & After Surgery in Patients With Resectable Gallbladder Cancer

PRIMARY OBJECTIVE:

I. To determine the difference in overall survival (OS) at 3 years for patients with
incidental gallbladder cancer (IGBC) who receive neoadjuvant gemcitabine hydrochloride
(gemcitabine) and cisplatin (gem/cis) prior to reoperation followed by adjuvant capecitabine
compared to patients who receive only adjuvant capecitabine after reoperation.

SECONDARY OBJECTIVES:

I. To determine the difference in recurrence-free survival (RFS) at 1 year for patients with
IGBC who receive perioperative chemotherapy prior to and after re-operation compared to
patients who receive only adjuvant chemotherapy after reoperation.

II. To assess the clinical effect of perioperative chemotherapy compared to only adjuvant
chemotherapy after reoperation on resectability among 3 cohorts: all enrolled patients, all
patients who undergo staging laparoscopy, and all patients who undergo laparotomy.

III. To compare the incidence of residual disease at the time of re-resection between
patients who receive perioperative chemotherapy and those who receive only adjuvant
chemotherapy.

OUTLINE: Participants are randomized to 1 of 2 arms.

ARM I: Participants undergo re-resection (including partial liver resection and portal lymph
node dissection) after incidental diagnosis of gallbladder cancer. Participants then receive
capecitabine orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 21 days for
8 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Participants receive cisplatin intravenously (IV) over 1 hour and gemcitabine IV over
30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of
disease progression or unacceptable toxicity. Within 10 weeks of chemotherapy, participants
undergo re-resection (including partial liver resection and portal lymph node dissection).
Participants then receive capecitabine PO BID on days 1-14. Treatment repeats every 21 days
for 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up periodically for up to 3
years.

Inclusion Criteria:

- Histologically-confirmed T1b, T2 or T3 gallbladder cancer discovered incidentally at
the time of or following routine cholecystectomy for presumed benign disease

- Resectable disease at the time of enrollment based on high-quality, preoperative,
cross-sectional imaging of the chest, abdomen, and pelvis (C/A/P)

- Enrollment and randomization within 12 weeks of initial cholecystectomy

- High-quality cross-sectional imaging (computed tomography [CT] or magnetic resonance
imaging [MRI]) performed within 4 weeks prior to enrollment

- Able to give informed consent

- Able to adhere to study visit schedule and other protocol requirements

- Eastern Cooperative Oncology Group (ECOG) performance status of < 2

- Absolute neutrophil count ≥ 1500/mm³

- Platelet count ≥ 100,000/mm³

Exclusion Criteria:

- Patients with histologically-confirmed Tis, T1a, or T4 tumors

- Unresectable gallbladder cancer at the time of enrollment based on high-quality,
preoperative, cross-sectional imaging of the C/A/P

- Unable to sign informed consent

- Serum creatinine > 1.5 x upper limit of normal or estimated creatinine clearance
(CrCl) < 45 ml/min

- Serum total bilirubin > 1.5 x upper limit of normal

- Presence of active infection

- Pregnant and/or breastfeeding

- Known dihydropyrimidine dehydrogenase deficiency