Bile Duct Cancer (Cholangiocarcinoma) Clinical Trials

About Bile Duct Cancer (Cholangiocarcinoma) trials

Cholangiocarcinoma trials are unusually molecularly actionable for a GI cancer, with multiple targeted-therapy approvals in the past few years based on tumor mutation testing. FGFR2 fusions and rearrangements occur in 10-15% of intrahepatic cholangiocarcinoma and gate eligibility for FGFR inhibitor trials, with several approved agents already in clinical use. IDH1 mutations occur in roughly 15% of intrahepatic cholangiocarcinoma and gate IDH1 inhibitor trials; IDH2 mutations are uncommon but covered. BRAF V600E mutations are rare but actionable for targeted combinations. HER2 (ERBB2) amplification, present in around 5-15% of cholangiocarcinoma, gates anti-HER2 ADC and antibody trials. MMR deficiency is uncommon but qualifies the rare patient for immunotherapy trials. PD-L1 (CD274) is used in some IO trial designs, although IO is now standard front-line regardless. KRAS and FGFR3 are tested less for direct eligibility and more for trial stratification or to rule out other targets.

Recruiting trials in cholangiocarcinoma organize along anatomic site, mutation status, and treatment line. Front-line trials test additions to or alternatives to gemcitabine + cisplatin + IO, the post-TOPAZ-1 standard for advanced disease. Targeted trials are organized by mutation: FGFR2-fusion trials test next-generation FGFR inhibitors (including agents designed to overcome resistance to first-generation inhibitors), IDH1 trials test combinations with IDH inhibitors and second-generation inhibitors, HER2 trials test anti-HER2 ADCs and bispecifics, and BRAF V600E trials test targeted combinations. Second-line trials in mutation-negative patients test novel mechanisms, ADCs, and IO combinations. Adjuvant trials test additions to capecitabine. Locally advanced trials test chemoradiation strategies and surgical conversion approaches. Intrahepatic and extrahepatic cholangiocarcinoma sometimes share trials and sometimes have separate cohorts based on biology and surgical considerations.

Common eligibility filters in cholangiocarcinoma trials include anatomic site, mutation status, and prior targeted-therapy exposure. Anatomic site (intrahepatic, perihilar, distal extrahepatic, or gallbladder) gates many trials and influences trial design. Mutation status testing is foundational because many trials are mutation-restricted: FGFR2 fusion confirmation for FGFR trials, IDH1 mutation for IDH trials, HER2 amplification for HER2 trials. Prior FGFR inhibitor exposure for FGFR2-fusion patients (and which generation) matters for next-line trial design. Prior IDH inhibitor exposure for IDH1-mutant patients is similarly relevant. Liver function (bilirubin, albumin, INR) and biliary drainage status are screened on most trials, with many requiring stable post-stenting biliary drainage and bilirubin within trial-specific limits. Performance status, with most trials accepting ECOG 0-1, sometimes ECOG 2.

Biomarkers tested in Bile Duct Cancer (Cholangiocarcinoma) trials

These are the molecular markers most commonly required or evaluated in Bile Duct Cancer (Cholangiocarcinoma) eligibility criteria. OncoMatch extracts them from each trial's protocol and matches them against your test results.