An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma (ProvIDHe)

An Open-Label Early Access Phase 3b Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma

A Phase 3b research study to consolidate the data that ivosidenib is safe and effective in adult patients with previously treated, locally advanced, or metastatic cholangiocarcinoma (CCA). All patients who meet inclusion criteria will be enrolled to receive ivosidenib tablets orally once daily for 28 day cycles, continuing as long as clinical benefit and consent for participation is maintained. There will be a minimum of 6 study visits from screening until the final follow-up, if one cycle of treatment is completed and consent is maintained through 18 months of follow-up. Each additional cycle completed will add one study visit, on the first day of each cycle.

Study Overview

• Status: Recruiting
• Conditions: Cholangiocarcinoma
• Intervention / Treatment: Drug: Ivosidenib Oral Tablet

Detailed Description

Ivosidenib is approved in the United States and in EU for the treatment of advanced or metastatic CCA; this study is being conducted to conslidate the data related to the safety, efficacy, and impact on quality of life for patients. This is an open-label, single-arm study of ivosidenib, which means that all patients meeting eligibility criteria will receive two 250 mg ivosidenib tablets, totaling 500mg of drug, to be taken orally, once daily, for 28 consecutive days, also referred to as one cycle. Additional cycles can continue as long as clinical benefit is confirmed by an investigator, and consent is maintained. There will be a screening visit, study visit on day 1 of each cycle, withdrawal visit within 42 days of stopping treatment, and a follow-up visit every 6 months for up to 18 months after stopping treatment. This results in a minimum of 6 study visits for the completion of one 28-day cycle of ivosidenib. One additional study visit will be added on day one of each additional cycle of treatment. Study visits will include an electrocardiogram (ECG), physical exam, tumor assessment, according to local practive at a given site and blood and urine analyses. If at any point ivosidenib is made available as a medical prescription at the patient's site, patients will be withdrawn from the study treatment and patients will be followed to collect data on overall survival.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Institut de Recherches Internationales Servier, Clinical Studies Department; Phone Number: +33 1 55 72 60 00; Email: scientificinformation@servier.com

Study Locations

• Armenia
  • Yerevan, Armenia
    • Completed
    • Erebouni MC
  • Yerevan, Armenia
    • Completed
    • National Center of Oncology of Ra M
• Australia
  • Brisbane, Australia
    • Completed
    • Royal Brisbane & Women's Hospital
  • Fitzroy, Australia
    • Completed
    • St Vincent's Hospital
  • Subiaco, Australia
    • Completed
    • St John of God Hospital - Bendat Family Comprehensive Cancer Centre (BFCCC)
  • Sydney, Australia
    • Completed
    • Kinghorn Cancer Centre
  • Woodville, Australia
    • Completed
    • The Queen Elizabeth Hospital
• Austria
  • Graz, Austria
    • Completed
    • Medizinische Universitaet Graz
  • Linz, Austria
    • Completed
    • Ordensklinikum Linz GmbH
  • Salzburg, Austria
    • Completed
    • Universitaetsklinik fuer Innere Medizin III, mit Hämatologie, internistischer Onkologie, Hämostaseologie, Infektiologie, Rheumatologie und Onkologisches Zentrum
  • Vienna, Austria
    • Completed
    • Medizinische Universitaet Wien Universitaetsklinik fuer Innere Medizin I
• Belgium
  • Brussels, Belgium
    • Completed
    • Universite Libre de Bruxelles ULB -
  • Ghent, Belgium
    • Completed
    • Universitair Ziekenhuis Gent UZ Gent
  • Leuven, Belgium
    • Completed
    • UZ Leuven
  • Woluwe-Saint-Lambert, Belgium
    • Completed
    • Cliniques Univ St Luc - Gastro-Enterology
• Canada
  • Calgary, Canada
    • Completed
    • Tom Baker Cancer Center
  • Halifax, Canada
    • Completed
    • NSHA, QEII Health Sciences Centre
  • London, Canada
    • Completed
    • London Regional Cancer Program
  • Toronto, Canada
    • Completed
    • Princess Margaret Cancer Center
  • Toronto, Canada
    • Completed
    • Sunnybrook Health Sciences Centre
• France
  • Lyon, France
    • Completed
    • Hopital Prive Jean Mermoz
  • Marseille, France
    • Completed
    • Hôpital de la Timone
  • Montpellier, France
    • Completed
    • CHU Montpellier
  • Nantes, France
    • Completed
    • Centre Hospitalier Universitaire de Nantes CHU de Nantes
  • Paris, France
    • Completed
    • Institute Mutualiste Montsouris
  • Pessac, France
    • Completed
    • CHU Bordeaux, Hopital Haut-Leveque
  • Poitiers, France
    • Completed
    • CHU de Poitiers
• Germany
  • Berlin, Germany
    • Completed
    • Charite Universittsmedizin Berlin
  • Dresden, Germany
    • Completed
    • Universitaetsklinikum Carl-Gustav-Carus
  • Düsseldorf, Germany, 40225
    • Completed
    • Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
  • Frankfurt, Germany
    • Completed
    • Universitaetsklinikum Frankfurt
  • Freiburg im Breisgau, Germany
    • Completed
    • Medizinische Fakultaet der Universitaet Freiburg
  • Hanover, Germany
    • Completed
    • Medizinische Hochschule Hannover
  • München, Germany
    • Completed
    • Klinikum der Universitaet Muenchen-Grosshadern
• Ireland
  • Cork, Ireland
    • Completed
    • Cork University Hospital
  • Dublin, Ireland
    • Completed
    • St. James Hospital
  • Dublin, Ireland
    • Completed
    • St. Vincent's Private Hospital
• Italy
  • Bologna, Italy
    • Completed
    • Policlinico S. Orsola-Malpighi
  • Florence, Italy
    • Completed
    • AOU Careggi
  • Milan, Italy
    • Completed
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy
    • Completed
    • Ospedale San Raffaele
  • Napoli, Italy
    • Completed
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale
  • Reggio Emilia, Italy
    • Completed
    • IRCCS Arcispedale Santa Maria Nuova
  • Roma, Italy
    • Completed
    • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Rozzano, Italy
    • Completed
    • Humanitas Research Hospital
  • San Giovanni Rotondo, Italy
    • Completed
    • Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Casa Sollievo della Sofferenza (CSS)
  • Turin, Italy
    • Completed
    • A.O.U. Città della Salute e Della Scienza di Torino
  • Verona, Italy
    • Completed
    • AOUI Verona - Ospedale Borgo Roma
• Japan
  • Kanagawa, Japan
    • Recruiting
    • Kanagawa Cancer Center
  • Kumamoto, Japan
    • Recruiting
    • Kumamoto University Hospital
  • Matsuyama, Japan
    • Recruiting
    • Shikoku Cancer Center
  • Osaka, Japan
    • Recruiting
    • Osaka International Cancer Institution
  • Sapporo, Japan
    • Recruiting
    • Hokkaido University Hospital
  • Tokyo, Japan
    • Recruiting
    • National Cancer Center Hospital
• Netherlands
  • Amsterdam, Netherlands
    • Completed
    • Amsterdam UMC, location AMC
  • Limburg, Netherlands
    • Completed
    • Universiteit Maastricht UM - Maastricht University Medical Centre MUMC
• Romania
  • Bucharest, Romania
    • Completed
    • Institutul Clinic Fundeni
  • Cluj-Napoca, Romania
    • Completed
    • Regional Institute of Gastroenterology and Hepatology
  • Craiova, Romania
    • Completed
    • Centrul de Oncologie Sfantu Necta
  • Otopeni, Romania
    • Completed
    • Radiotherapy Center Cluj
  • Ploieşti, Romania
    • Completed
    • Municipal Hospital Ploiesti
• South Korea
  • Seongnam, South Korea
    • Completed
    • CHA Bundang Medical Center
  • Seoul, South Korea
    • Completed
    • Samsung Medical Center
  • Seoul, South Korea
    • Completed
    • Asan Medical Center
  • Seoul, South Korea
    • Completed
    • Seoul National University
  • Seoul, South Korea
    • Completed
    • Yonsei University Health System
• Spain
  • A Coruña, Spain
    • Completed
    • Complejo Hospitalario Universitario A Coruña (CHUAC)
  • Barcelona, Spain
    • Completed
    • Hospital Universitari Vall d'Hebron/Vall Hebron Institute of Oncology (VHIO)
  • Córdoba, Spain
    • Completed
    • Hospital Universitario Reina Sofa
  • Elche, Spain
    • Completed
    • Hospital General de Elche
  • Madrid, Spain
    • Completed
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Completed
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain
    • Completed
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain
    • Completed
    • Hospital Universitario HM Sanchinarro
  • Pamplona, Spain
    • Completed
    • Hospital Universitario de Navarra
  • Santander, Spain
    • Completed
    • Hospital Universitario Marqués de Valdecilla
• Sweden
  • Gothenburg, Sweden
    • Completed
    • Sahlgrenska University Hospital
  • Stockholm, Sweden
    • Completed
    • Karolinska University Hospital
• United Kingdom
  • Birmingham, United Kingdom
    • Completed
    • University Hospitals Birmingham (UHB) NHS Foundation Trust - Queen Elizabeth Hospital Birmingham (QEHB)
  • Glasgow, United Kingdom
    • Completed
    • The Beatson Institute West of Scotland Cancer Research
  • London, United Kingdom
    • Completed
    • Imperial College London
  • London, United Kingdom
    • Completed
    • University College London Hospital NHS Trust
  • Manchester, United Kingdom
    • Completed
    • The Christie NHS Foundation Trust
  • Newcastle upon Tyne, United Kingdom
    • Completed
    • The Newcastle Upon Tyne Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of nonresectable or metastatic Cholangiocarcinoma (CCA), not eligible for curative-intent resection, transplantation, or ablative therapies
• Have a documented IDH1 R132C, R132L, R132G, R132H, or R132S gene-mutated disease
• Have tried at least 1 prior type of systemic therapy for CCA, and have recovered from any side effects
• Female patients of childbearing potential must have a negative blood pregnancy test prior to starting treatment and must agree to use 2 forms of contraception from the time they enroll to 1 month after their last dose of study drug
• Male patients with a female partner with childbearing potential must also agree to use 2 forms of contraception from the time they enroll to 1 month after their last dose of study drug

Exclusion Criteria:

• Received a prior IDH1 inhibitor
• Have received a transplant
• Have received systemic cancer treatment or radiotherapy within 2 weeks prior to Day 1 of Cycle 1
• Have received hepatic radiation, chemoembolization, and radiofrequency ablation within 4 weeks prior to Day 1 of Cycle 1
• Have ongoing brain metastases requiring steroids
• Have underwent major surgery within 4 weeks of Day 1 of Cycle 1 prior to C1D1
• Have an active hepatitis B (HBV) or hepatitis C (HCV) infections, known positive human immunodeficiency virus (HIV) antibody results, or acquired immunodeficiency syndrome (AIDS) related illness
• Are pregnant or breastfeeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ivosidenib; Ivosidenib 500 mg, taken orally as two 250 mg tablets once daily for an unlimited amount of continuous 28-day cycles	Drug: Ivosidenib Oral Tablet; Ivosidenib 500 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events (AEs) from Day 1 of Cycle 1 through 28 days after last study treatment	AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. All reported AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA), using the latest version.	Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
Number of Serious Adverse Events (SAEs) during the study treatment period (from Day 1 of Cycle 1 through the last study treatment intake or withdrawal of consent, whichever comes first).	SAEs related to study drug will be collected irrespective of the time of onset. AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment, 6 months after last study treatment, 12 months after last study treatment, 18 months after last study treatment
Number of QT prolongation events during electrocardiogram (ECG) assessed as Grade 2 or worse occurring from Day 1 of Cycle 1 through 28 days after last study treatment	QT interval, using Fridericia's formula [QTcF], to average QTc interval > 480 to 500msec (Grade 2) or worse, as seen during an ECG. This is classified as an Adverse Event of Special Interest (AESI) for this study.	Day 1 of cycle 1, week 2 of cycle 1, week 3 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
Change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score from baseline to worst value out of the post-baseline assessments.	ECOG PS scoring consists of Grade 0 - 5, with 0 being the patient is fully active and 5 being the patient is dead. Descriptive statistics of ECOG PS over time will be summarized by frequency. Shift tables may be provided for ECOG PS from baseline to worst value of post-baseline assessments.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Number of Adverse Events (AEs) leading to discontinuation or death from day 1 through 28 days after the last study treatment	Total number of AEs that result in discontinuation from treatment or death. AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.	Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
Total laboratory abnormalities using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grading scale or the low/normal/high classifications based on laboratory normal ranges.	Listing of all laboratory hematology, coagulation, and chemistry data with values flagged as abnormal to show the corresponding NCI-CTCAE grades and the classifications relative to the laboratory normal ranges.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Change from baseline to the worst on-treatment value of laboratory abnormalities.	Abnormalities will be classified by using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grading scale or the low/normal/high classifications based on laboratory normal ranges. Shift tables using NCI-CTCAE grades to compare baseline to the worst on-treatment value will be used. For laboratory tests, including hematology, coagulation, and chemistry, where NCI-CTCAE grades are not defined, shift tables using the low/normal/high [low and high] classification to compare baseline to the worst on treatment may be generated. On-treatment is considered from Day 1 of Cycle 1 through 28 days after the last dose.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Number of patients with vital sign values outside limits of the normal range at each time point.	Vital signs include systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Mean change from baseline values to the worst on-treatment value of patients with vital signs outside limits of the normal range	On-treatment is considered from Day 1 of Cycle 1 through 28 days after the last dose. Vital signs include systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from date of enrollment to the date of death due to any cause. It will be assessed using the Kaplan-Meier (KM) method curves and estimates.	through 28 days after last treatment
Duration of response (DOR)	DOR is defined as the time from the date of response to either progression or death. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.	through 28 days after last treatment
Time to response (TTR)	TTR is defined as the time from the date of enrollment to the date of response. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.	through 28 days after last treatment
Proportion of days at home or hospital for all patients		through 28 days after last treatment
Change from baseline of health economic measures, as assessed by the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5).	Health economic measures, as assessed by the EQ-5D-5L, will be evaluated for patients with a baseline assessment and at least 1 post-baseline EQ-5D-5L assessment that generate a score. Change from baseline scores for each time point will be quantified with descriptive statistics.	through 28 days after last treatment
Progression-free survival (PFS) time beginning at enrollement	PFS is defined as the time from the date of enrollment to the date at which the disease escalates or progresses. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.	through 28 days after last treatment
Change from baseline of Quality of life scores	Measured by the validated European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21). EORTC QLQ-BIL21, will be evaluated for patients with a baseline assessment and at least 1 post-baseline QLQ-BIL21 assessment that generates a score. Change from baseline for each time point, will be summarized using descriptive statistics.	through 28 days after last study treatment

Collaborators and Investigators

• Sponsor: Servier Affaires Médicales

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: May 17, 2023
• First Submitted That Met QC Criteria: May 17, 2023
• First Posted (Actual): May 25, 2023

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: CCA; Pretreated locally advanced or metastatic cholangiocarcinoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cholangiocarcinoma; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; ivosidenib
• Other Study ID Numbers: DIM-95031-002; 2022-501463-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.

Access can be requested for all interventional clinical studies:

• used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
• where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

• sponsored by Servier
• with a first patient enrolled as of 1 January 2004 onwards
• for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

• IPD Sharing Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• IPD Sharing Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes