27 Ampullary Cancer Clinical Trials Recruiting Now (July 2026): Periampullary, FOLFOX, Pembrolizumab, MSI

Last updated: July 1, 2026

Current Clinical Trial Landscape

Recruiting Trials by Treatment Setting

Neoadjuvant / Resectable

Before or instead of upfront surgery:

• NCT07081360 - Neoadjuvant vs upfront surgery for resectable periampullary cancer (Phase 3)
• NCT06801899 - Total vs partial pancreaticoduodenectomy (surgery-type trial applying to periampullary tumors requiring Whipple)

Adjuvant (After Resection)

Reducing recurrence risk after curative surgical resection — the only setting with a recently-launched ampullary-specific Phase 3:

• NCT06813976 - AMPIRINOX (PRODIGE 98): modified FOLFIRINOX vs capecitabine or gemcitabine adjuvant chemotherapy in resected ampullary adenocarcinoma (Phase 3, French-PRODIGE multicenter). First dedicated ampullary-adenocarcinoma adjuvant chemo Phase 3 — current standard adjuvants (capecitabine, gemcitabine) are extrapolated from pancreatic/biliary trials, not validated in ampullary specifically.

Metastatic / Advanced

For unresectable or metastatic disease — biliary-tract Phase 3 trials + biomarker-selected tumor-agnostic baskets apply when standard ampullary protocols (FOLFOX, FOLFIRINOX, gem/cis) have been exhausted:

• NCT06333314 - Dostarlimab for dMMR/MSI-H solid tumors (tumor-agnostic basket; ~5-10% of ampullary tumors are MSI-H)
• NCT07221253 - Rilvegostomig or durvalumab + chemo for 1L biliary tract cancer (Phase 3, activated 2026-06 — biliary-tract eligible includes ampullary adenocarcinoma per most 1L biliary protocol definitions)
• NCT06467357 - T-DXd + rilvegostomig vs SoC in advanced HER2-expressing biliary tract cancer (Phase 3, activated 2026-06 — HER2+ ampullary eligible)
• NCT06622057 - D07001 softgel capsules + capecitabine in advanced biliary tract cancer (Phase 3, activated 2026-06)

Trials by Treatment Approach

Immunotherapy

Checkpoint inhibitors for biomarker-selected patients:

• NCT06333314 - Dostarlimab for dMMR/MSI-H (Phase 2)

KRAS-Targeted Therapy

KRAS mutations are common in ampullary cancer (~30-40% of intestinal-type, ~15-25% of pancreaticobiliary-type ampullary). Pan-RAS(ON) and variant-selective KRAS inhibitor trials are typically tumor-agnostic baskets — they enroll KRAS-mutated ampullary patients but list NSCLC/CRC/PDAC as primary conditions in their registrations. Worth asking your oncologist whether a KRAS-targeted basket trial enrolling ampullary is open at your center. No ampullary-specific KRAS-targeted Phase 3 recruiting in 2026.

Targeted Therapy (HER2-Mutation Baskets)

• NCT06760819 - Sevabertinib (BAY 2927088, reversible HER2 tyrosine kinase inhibitor) Phase 2 basket study in HER2-mutation-positive advanced solid tumors. Tumor-agnostic enrollment; HER2 mutation rate in ampullary cancer is ~5-10%, making this a relevant basket option for HER2-mutated patients.

Surgical Approaches

• NCT06801899 - Total vs partial pancreaticoduodenectomy (broad PD-eligible adenocarcinoma)
• NCT07328607 - Laparoscopic vs open pancreaticoduodenectomy
• NCT05116072 - TPIAT for resectable adenocarcinoma (pancreas head region; includes periampullary)
• NCT05843877 - XandTX: Pancreatic head resection vs total pancreatectomy + islet autotransplantation in periampullary cancer with high-risk profile for postoperative pancreatic fistula (Phase 3, TU Dresden). Compares preservation surgery vs total pancreatectomy with autologous islet preservation in high-fistula-risk patients.

Chemotherapy Optimization

• NCT05780684 - Individualized 5-FU dose escalation

View all 23 ampullary cancer trials on ClinicalTrials.gov →

Frequently Asked Questions