Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation
NCT ID: NCT06501625
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
52 participants
INTERVENTIONAL
2024-12-16
2027-09-13
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Safety Lead-In Phase
Ivosidenib
Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration
Durvalumab (for the first 8, 21-day, cycles)
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles
Gemcitabine (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
Cisplatin (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
Durvalumab (starting from cycle 9)
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.
Expansion Phase
Durvalumab (for the first 8, 21-day, cycles)
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles
Gemcitabine (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
Cisplatin (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
Durvalumab (starting from cycle 9)
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.
Ivosidenib Recommended Combination Dose (RCD)
RCD administered orally once daily, taken continuously throughout treatment duration
Interventions
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Ivosidenib
Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration
Durvalumab (for the first 8, 21-day, cycles)
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles
Gemcitabine (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
Cisplatin (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
Durvalumab (starting from cycle 9)
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.
Ivosidenib Recommended Combination Dose (RCD)
RCD administered orally once daily, taken continuously throughout treatment duration
Eligibility Criteria
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Inclusion Criteria
* Have documented IDH1 gene-mutated cholangiocarcinoma based on local or central laboratory testing (R132C/L/G/H/S mutation variants tested).
* Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
* Have adequate bone marrow function as evidenced by:
* Absolute neutrophil count ≥ 1,500/mm3 or 1.5 ×109/L
* Hemoglobin ≥ 9 g/dL
* Platelet count ≥ 100,000/mm3 or 100 × 109/L
* Have adequate hepatic function as evidenced by:
* Serum bilirubin ≤ 2.0 × the upper limit of normal (ULN); this will not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before randomization
* Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5 × ULN; for patients with hepatic metastases, ALT and AST ≤ 5.0 × ULN
* Have adequate renal function, defined as: creatinine clearance \> 60 mL/min per 24 hour urine or as calculated on the Cockcroft-Gault formula (using actual body weight):
Creatine CL (mL/min)= (140 - Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine (mg/dL)
* Patients with Grade ≥2 neuropathy to be evaluated on a case-by-case basis after consultation with the medical monitor
* Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
* Participation in another interventional study at the same time or within 14 days prior to the first study medication (triple combination treatment) administration. For patients having participated to another prior interventional study, the first dose of ivosidenib should occur after a period greater than or equal to 5 half-lives or 28 days, whichever is shorter of the last dose of the prior investigational product.
* Active or prior documented autoimmune or inflammatory disorders including:
* inflammatory bowel disease (e.g., colitis or Crohn's disease)
* diverticulitis (with the exception of diverticulosis)
* systemic lupus erythematosus
* Sarcoidosis syndrome
* Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)
Note: in cases with no active disease for ≥ 5 years, patients may be considered for inclusion if approved by the Medical Monitor. Participants with the following conditions are eligible for the study:
* chronic skin condition that does not require systemic therapy
* vitiligo
* alopecia
* hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy
* unmedicated celiac disease that is controlled by diet
* Have heart rate-corrected QT interval using Fridericia's formula (QTcF) of ≥ 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome/sudden death, polymorphic ventricular arrhythmia). The Sponsor should review participants with bundle branch block and prolonged QTcF for potential inclusion.
* Have an active infection, including:
* Hepatitis B (clinical evaluation includes: presence of hepatitis B surface antigen \[HBsAg\] and/or anti-HBcAb with detectable hepatitis B virus \[HBV\] DNA ≥ 10 IU/mL)
* Hepatitis C
* Tuberculosis (clinical evaluation includes: clinical history, physical examination and/or radiographic findings, and tuberculosis testing as per local practice)
* Human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2 antibodies) Note: Patients with a resolved or past HBV infection (i.e., presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) do not need to be excluded from the study. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.
Exclusion Criteria
* Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before study participation. Note: For the Safety Lead-In Phase, participants who received one prior cycle of durvalumab plus gemcitabine/cisplatin and required dose modifications for treatment-related toxicity are excluded.
* Patients who developed recurrent disease \> 6 months after surgery with curative intent, and, if given, \> 6 months after the completion of adjuvant (chemotherapy and/or radiation).
* Prior exposure to immune-mediated therapy, including, but not limited to, anti-PD-1or other anti-PD-L1, and anti-PD-L2, anti-CTLA-4 antibodies, excluding therapeutic anticancer vaccines.
18 Years
ALL
No
Sponsors
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Institut de Recherches Internationales Servier
OTHER
Responsible Party
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Locations
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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
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
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 Universitario Gregorio Marañón
Madrid, , Spain
H. 12 de Octubre
Madrid, , Spain
Hospital Universitario Fundación Jiménez Díaz
Madrid, , Spain
Countries
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Central Contacts
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Institut de Recherches Internationales Servier (I.R.I.S.) Clinical Studies Department
Role: CONTACT
Phone: +33 1 55 72 60 00
Email: [email protected]
Other Identifiers
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2024-514261-19-00
Identifier Type: CTIS
Identifier Source: secondary_id
S095031-210
Identifier Type: -
Identifier Source: org_study_id