EA2197 (OPT-IN) – Optimal Perioperative Therapy for Incidental Gallbladder Cancer (OPT-IN): A Randomized Phase II/III Trial

Gallbladder carcinoma (GBC) is a rare disease with a poor prognosis and an overall estimated five-year survival rate of 5%-13%. Most instances of gallbladder cancer are found incidentally, during, or after elective cholecystectomy for presumed benign disease. Current management guidelines for incidental GBC recommend re-resection for T1b, T2, and T3 lesions, to remove sites at risk for harboring residual disease. However, incidental GBC is characterized by poor tumor biology; at the time of re-operation, up to 75% of patients have residual locoregional disease, and 20% have disseminated disease. Both factors are strongly associated with inoperability and poor outcomes.

Chemotherapy with gemcitabine and cisplatin is standard-of-care therapy for GBC patients with advanced disease. Previous trials showed this regimen to be superior to gemcitabine alone for these patients. Neoadjuvant therapy has been associated with higher resectability rates and improved survival in some gastrointestinal malignancies, such as gastric and pancreas cancer. However, few studies have examined its impact on GBC outcomes, and none assess perioperative therapy in incidental GBC. EA2197 is the first randomized, phase II/III trial to do so.

This randomized clinical trial is for patients with histologically-confirmed stage T2 or T3 incidental GBC. Its primary objective is to determine the difference in overall survival for patients given neoadjuvant gemcitabine and cisplatin, re-resection, then adjuvant gemcitabine and cisplatin, compared to patients who receive only adjuvant gemcitabine and cisplatin after re-resection (usual treatment).

This study is led by Shishir Maithel, MD (Emory University).

Other National Clinical Trials Network (NCTN) groups are collaborating on this trial through study champions. The groups and their champions are the ALLIANCE for Clinical Trials in Oncology, Cristina Ferrone, MD (Dana-Farber/Harvard Cancer Center) and SWOG, Flavio Rocha, MD (Oregon Health & Science University).

Learn more about OPT-IN at ecog-acrin.org.