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
2 other identifiers
interventional
299
15 countries
79
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started May 2023
Longer than P75 for phase_3
79 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 3, 2023
CompletedFirst Submitted
Initial submission to the registry
May 17, 2023
CompletedFirst Posted
Study publicly available on registry
May 25, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2027
July 31, 2026
July 1, 2026
4.6 years
May 17, 2023
July 30, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
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 Outcomes (7)
Progression-free survival (PFS) time beginning at enrollement
through 28 days after last treatment
Overall survival (OS)
through 28 days after last treatment
Duration of response (DOR)
through 28 days after last treatment
Time to response (TTR)
through 28 days after last treatment
Change from baseline of Quality of life scores
through 28 days after last study treatment
- +2 more secondary outcomes
Study Arms (1)
Ivosidenib
EXPERIMENTALIvosidenib 500 mg, taken orally as two 250 mg tablets once daily for an unlimited amount of continuous 28-day cycles
Interventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (84)
Erebouni MC
Yerevan, Armenia
National Center of Oncology of Ra M
Yerevan, Armenia
Royal brisbane & Women's Hospital
Brisbane, Australia
St Vincent's Hospital
Fitzroy, Australia
St John of God Hospital - Bendat Family Comprehensive Cancer Centre (BFCCC)
Subiaco, Australia
Kinghorn Cancer Centre
Sydney, Australia
The Queen Elizabeth Hospital
Woodville, Australia
Medizinische Universitaet Graz
Graz, Austria
Ordensklinikum Linz GmbH
Linz, Austria
Universitaetsklinik fuer Innere Medizin III, mit Hämatologie, internistischer Onkologie, Hämostaseologie, Infektiologie, Rheumatologie und Onkologisches Zentrum
Salzburg, Austria
Medizinische Universitaet Wien Universitaetsklinik fuer Innere Medizin I
Vienna, Austria
Universite Libre de Bruxelles ULB -
Brussels, Belgium
Universitair Ziekenhuis Gent UZ Gent
Ghent, Belgium
UZ Leuven
Leuven, Belgium
Cliniques Univ St Luc - Gastro-Enterology
Woluwe-Saint-Lambert, Belgium
Tom Baker Cancer Center
Calgary, Canada
NSHA, QEII Health Sciences Centre
Halifax, Canada
London Regional Cancer Program
London, Canada
Princess Margaret Cancer Center
Toronto, Canada
Sunnybrook Health Sciences Centre
Toronto, Canada
Hôpital Privé Jean Mermoz
Lyon, France
Hopital de la Timone
Marseille, France
CHU Montpellier
Montpellier, France
Centre Hospitalier Universitaire de Nantes CHU de Nantes
Nantes, France
Institute Mutualiste Montsouris
Paris, France
CHU Bordeaux, Hôpital Haut-Lévêque
Pessac, France
CHU de Poitiers
Poitiers, France
Charite Universittsmedizin Berlin
Berlin, Germany
Universitaetsklinikum Carl-Gustav-Carus
Dresden, Germany
Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
Düsseldorf, 40225, Germany
Universitaetsklinikum Frankfurt
Frankfurt, Germany
Medizinische Fakultaet der Universitaet Freiburg
Freiburg im Breisgau, Germany
Medizinische Hochschule Hannover
Hanover, Germany
Klinikum der Universitaet Muenchen-Grosshadern
München, Germany
Cork University Hospital
Cork, Ireland
St. James Hospital
Dublin, Ireland
St. Vincent's Private Hospital
Dublin, Ireland
Policlinico S. Orsola-Malpighi
Bologna, Italy
AOU Careggi
Florence, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, Italy
Ospedale San Raffaele
Milan, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
Naples, Italy
IRCCS Arcispedale Santa Maria Nuova
Reggio Emilia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Roma, Italy
Humanitas Research Hospital
Rozzano, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Casa Sollievo della Sofferenza (CSS)
San Giovanni Rotondo, Italy
A.O.U. Città della Salute e della Scienza di Torino
Turin, Italy
AOUI Verona - Ospedale Borgo Roma
Verona, Italy
Kanagawa Cancer Center
Kanagawa, Japan
Kumamoto University hospital
Kumamoto, Japan
Shikoku Cancer Center
Matsuyama, Japan
Osaka International Cancer Institution
Osaka, Japan
Hokkaido University Hospital
Sapporo, Japan
National Cancer Center Hospital
Tokyo, Japan
Amsterdam UMC, location AMC
Amsterdam, Netherlands
Universiteit Maastricht UM - Maastricht University Medical Centre MUMC
Limburg, Netherlands
Institutul Clinic Fundeni
Bucharest, Romania
Regional Institute of Gastroenterology and Hepatology
Cluj-Napoca, Romania
Centrul de Oncologie Sfantu Necta
Craiova, Romania
Radiotherapy Center Cluj
Otopeni, Romania
Municipal Hospital Ploiesti
Ploieşti, Romania
CHA Bundang Medical Center
Seongnam, South Korea
Asan Medical Center
Seoul, South Korea
Samsung Medical Center
Seoul, South Korea
Seoul National University
Seoul, South Korea
Yonsei University Health System
Seoul, South Korea
Complejo Hospitalario Universitario A Coruña (CHUAC)
A Coruña, Spain
Hospital Universitari Vall d'Hebron/Vall Hebron Institute of Oncology (VHIO)
Barcelona, Spain
Hospital Universitario Reina Sofa
Córdoba, Spain
Hospital General de Elche
Elche, Spain
Hospital General Universitario Gregorio Maranon
Madrid, Spain
Hospital Universitario 12 de octubre
Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, Spain
Hospital Universitario HM Sanchinarro
Madrid, Spain
Hospital Universitario de Navarra
Pamplona, Spain
Hospital Universitario Marqués de Valdecilla
Santander, Spain
Sahlgrenska University Hospital
Gothenburg, Sweden
Karolinska University Hospital
Stockholm, Sweden
University Hospitals Birmingham (UHB) NHS Foundation Trust - Queen Elizabeth Hospital Birmingham (QEHB)
Birmingham, United Kingdom
The Beatson Institute West of Scotland Cancer Research
Glasgow, United Kingdom
Imperial College London
London, United Kingdom
University College London Hospital NHS Trust
London, United Kingdom
The Christie NHS Foundation Trust
Manchester, United Kingdom
The Newcastle Upon Tyne Hospitals
Newcastle upon Tyne, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Masking Details
- All patients, care providers, investigators, and outcomes assessors will know that each patient is taking the active study drug, ivosidenib.
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 17, 2023
First Posted
May 25, 2023
Study Start
May 3, 2023
Primary Completion (Estimated)
December 1, 2027
Study Completion (Estimated)
December 1, 2027
Last Updated
July 31, 2026
Record last verified: 2026-07
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorization in EEA or US if the study is used for the approval.
- 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.
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.