RecruitingPhase 1Phase 2NCT06501625

Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation

A Phase 1b/2, Safety Lead-in and Dose-Expansion, Open Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Durvalumab and Gemcitabine/Cisplatin as First-line Therapy in Participants With Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation


Sponsor

Institut de Recherches Internationales Servier

Enrollment

52 participants

Start Date

Dec 16, 2024

Study Type

INTERVENTIONAL

Conditions

Summary

The objective of this study is to investigate the safety, tolerability and preliminary activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin as first-line therapy in participants with locally advanced, unresectable or metastatic cholangiocarcinoma with an IDH1 mutation. The study will begin with a safety lead-in phase (Phase 1b study) to determine the recommended combination dose (RDC) and then will transition to an expansion phase (Phase 2 study) to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1, on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through 8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90 days after treatment has ended, safety follow-up visits will occur and then participants will be followed for survival every 3 months. Study visits may include blood tests, ECG, vital signs, and a physical examination.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study tests a combination of three drugs — ivosidenib (a targeted therapy), durvalumab (an immunotherapy), and standard gemcitabine/cisplatin chemotherapy — as a first-line treatment for bile duct cancer (cholangiocarcinoma) that has a specific genetic mutation called IDH1. **You may be eligible if...** - You have confirmed locally advanced or metastatic cholangiocarcinoma (bile duct cancer) - Your cancer has been tested and found to carry an IDH1 mutation - You have not received prior treatment for advanced disease (or only one cycle of durvalumab + gemcitabine/cisplatin) - You have measurable disease on imaging - Your blood counts, liver, and kidney function meet acceptable levels **You may NOT be eligible if...** - You have received prior immunotherapy (anti-PD-1, anti-PD-L1, or anti-CTLA-4) - You have active autoimmune or inflammatory disorders (such as inflammatory bowel disease or lupus) - You have active hepatitis B, hepatitis C, tuberculosis, or HIV - You have a heart rhythm abnormality (prolonged QT interval) or significant heart failure - You have unresolved side effects (grade 2 or higher) from prior treatments - You are currently in another interventional study Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGIvosidenib

Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration

DRUGDurvalumab (for the first 8, 21-day, cycles)

1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles

DRUGGemcitabine (for the first 8, 21-day, cycles)

1000 mg/m2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

DRUGCisplatin (for the first 8, 21-day, cycles)

25 mg/m\^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

DRUGDurvalumab (starting from cycle 9)

1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.

DRUGIvosidenib Recommended Combination Dose (RCD)

RCD administered orally once daily, taken continuously throughout treatment duration


Locations(37)

Usc Norris Comprehensive Cancer Center

Los Angeles, California, United States

Northwestern Medicine

Chicago, Illinois, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Duke University

Durham, North Carolina, United States

Gibbs Cancer Center

Spartanburg, South Carolina, United States

Tennesse Oncology - Elliston Place Plaza

Nashville, Tennessee, United States

The University of Texas Md Anderson Cancer Center

Houston, Texas, United States

Alfred Health

Melbourne, Australia

Hospital de Amor - Barretos

Barretos, Brazil

Oncoclinicas Mg

Belo Horizonte, Brazil

CIONC

Curitiba, Brazil

Instituto Dor de Pesquisa E Ensino Sp

São Paulo, Brazil

Princess Margaret Cancer Centre

Toronto, Canada

Institut Bergonie

Bordeaux, France

Hôpital Beaujon

Clichy, France

Chu Montpellier-Hopital Saint-Eloi

Montpellier, France

Charite Universitatsmedizin

Berlin, Germany

Universitätsklinikum Düsseldorf

Düsseldorf, Germany

Universitären Centrums Für Tumorerkrankungen (Uct) Der J.W. Goethe-Universität Frankfurt

Frankfurt, Germany

Medizinische Hochschule Hannover Oe 6810

Hanover, Germany

Universitätsklinikum Ulm

Ulm, Germany

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

National Cancer Center Hospital

Chūōku, Japan

Kyoto University Hospital

Kyoto, Japan

Kanagawa Cancer Center

Yokohama, Japan

Cha Bundang Medical Center

Seongnam, South Korea

Seoul National University Bundang Hospital

Seongnam, South Korea

Asan Medical Center

Seoul, South Korea

Samsung Medical Center

Seoul, South Korea

Seoul National University Hospital

Seoul, South Korea

Severance

Seoul, South Korea

Seoul St. Mary'S Hospital

Seoul, South Korea

H. Valle de Hebron

Barcelona, Spain

Hospital Clinic de Barcelona

Barcelona, Spain

Hospital Universitario Gregorio Marañón

Madrid, Spain

H. 12 de Octubre

Madrid, Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

View Full Details on ClinicalTrials.gov

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NCT06501625