Observational Study of Ivosidenib Treatment for Advanced or Metastatic Bile Duct Cancer with the IDH1-R132 Mutation

In cholangiocarcinoma (bile duct cancer), malignant tumors develop in the bile ducts—that is, in the tiny channels that carry bile from the liver to the intestine (duodenum). In some of these tumors, a mutation is found in the IDH1 gene at position R132. This genetic mutation alters the function of the affected enzyme, leading to increased production of 2-hydroxyglutarate, which can promote the growth of cancer cells. The active ingredient ivosidenib is a so-called IDH1 inhibitor that specifically binds to the altered (mutated) IDH1 enzyme and inhibits its activity, thereby inhibiting cancer growth. In May 2023, the European Medicines Agency (EMA) approved ivosidenib as a monotherapy for adult patients with locally advanced or metastatic cholangiocarcinoma with an IDH1 R132mutation who had previously received at least one systemic therapy. It is taken once daily as a tablet.

The aim of this observational study is to observe, under real-world conditions, how treatment with the active ingredient ivosidenib proceeds in patients with an IDH1-R132mutation proceeds in routine clinical practice, and to assess how effective and well-tolerated treatment with ivosidenib is in patients with IDH1 R132-mutated bile duct cancer. To this end, data will be collected specifically on disease progression—including time to disease progression, overall survival, time to treatment discontinuation, and tumor response to therapy. In addition, data on quality of life during treatment will be collected. This is a prospective, multicenter study. The treating study physicians decide on treatment with ivosidenib independently of the study. Subsequently, data is collected on how the therapy proceeds in routine clinical practice. Because treatment is not assigned by the study, there is no randomization into groups and no blinding. Approximately 100 patients are expected to participate. In addition, patients may voluntarily participate in an optional questionnaire section on quality of life, which is conducted in German.

Eligible participants are patients aged 18 and older with histologically confirmed locally advanced or metastatic cholangiocarcinoma in which an IDH1-R132 mutation has been detected. Another requirement is that the patient has already received at least one prior course of drug therapy and that a decision has been made to treat them with ivosidenib.