A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

A Phase 2, Open-label, Multicenter Study of Orally Administered Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT06081829

Enrollment

Registered

2023-10-13

Start date

2023-10-10

Completion date

2027-05-31

Last updated

2025-12-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cholangiocarcinoma Metastatic, Cholangiocarcinoma Non-resectable

Keywords

IDH-1 Mutation, Cholangiocarcinoma Non-resectable with an IDH-1 Mutation, Cholangiocarcinoma Metastatic with an IDH-1 Mutation

Brief summary

This study will enroll participants with nonresectable or metastatic cholangiocarcinoma with an Isocitrate dehydrogenase protein, 1 (IDH1) mutation, who have previously received at least 1, but no more than 2, prior regimens for advanced disease. All participants will receive ivosidenib daily throughout multiple 28 day cycles. Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met. Study visits will be conducted every week during Cycle 1 (Days 1, 8, 15, and 22), every other week during Cycles 2 and 3, and Day 1 of each cycle thereafter. After the last dose of treatment, participants will attend an end of treatment and a post-treatment follow-up visit, and participants will be followed to assess overall survival. Study visits may include a tumor assessment, physical exam, electrocardiogram (ECG), blood and urine analysis, and questionnaires.

Interventions

DRUGIvosidenib

Subjects will take 2 tablets (500 mg total) orally once daily.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Have nonresectable or metastatic cholangiocarcinoma and are not eligible for curative resection, transplantation or ablative therapies * Have documented IDH1 gene-mutated disease from a tumor biopsy * Have an ECOG PS score of 0 or 1 * Have an expected survival of 3 months or more * Have at least one evaluable and measurable lesion * Have disease progression following the most recent of 1 or 2 prior systemic regimens for advanced disease with progression on the treatment that was most recently given at a minimum, and must have received at least 1 gemcitabine- or 5-FU -containing regimen * Have recovered from side effects associated with the prior treatment therapy * Have adequate bone marrow function * Have adequate hepatic (liver) and renal (kidney) function * Women of child bearing potential must have a negative serum pregnancy test before starting study treatment, and use birth control during the study and for 90 days after the last dose of ivosidenib * Fertile men with female partners of child bearing potential must use birth control during the study and for 90 days after the last dose of ivosidenib

Exclusion criteria

* Received a prior IDH inhibitor. * Have known symptomatic brain metastases requiring steroids. * Pregnancy, possibility of becoming pregnant during the study and breast-feeding women or woman who plans to restart breast-feeding after the study drug administration/intake. * Are taking known strong cytochrome P450 (CYP) 3A4 inducers or sensitive CYP3A4 substrate medications with a narrow therapeutic window * Have significant heart disease, including congestive heart failure, myocardial infarction (heart attack) unstable angina (chest pain) and/or stroke, within 6 months before starting the study * Have a heart-rate corrected QT interval ≥450 msec or other factors that increase the risk of QT prolongation or arrhythmic events * . Have active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis (paralysis of the stomach), or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. * Have known medical history of progressive multifocal leukoencephalopathy (PML)

Design outcomes

Primary

Measure	Time frame	Description
6-month Progression Free Survival (PFS) Rate	Through 6 months after the first dose	Proportion of subjects who are alive and progression-free (using RECIST v1.1) at 6 months after Day 1 (C1D1) per Independent Radiology Center (IRC)

Secondary

Measure	Time frame	Description
Overall Survival (OS)	Approximately 1 year	—
Objective Response (OR) Rate	Approximately 1 year	Complete response or partial response
Duration of Response (DOR)	Approximately 1 year	The time from date of first documented confirmed complete response (CR) or confirmed partial response (PR) to date of first documented disease progression or death due to any cause
Time to Response (TTR)	Approximately 1 year	The time from Day 1 to date of first documented confirmed complete response (CR) or confirmed partial response (PR)
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Baseline and 1 year	The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30) is comprised of 5 functional scales ((Physical functioning, Role functioning, Cognitive functioning, Emotional functioning and Social functioning), 3 symptom scales (Fatigue, Pain and Nausea/Vomiting), 6 additional single items (Dyspnoea, Insomnia, Appetite Loss, Constipation, Diarrhoea and Financial Difficulties) and global health status (GHS). All of the scale scores range from 0 - 100; for the functional scales and GHS the higher score represents better functioning and for the symptom scales and single items the higher score represents an increase in symptoms. .
Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-BIL21 Questionnaire Scores.	Baseline and 1 year	The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (EORTC-QLQ-BIL21) scores range from 0 - 100 with higher scores representing more severe symptoms.
Average EQ-5D-5L VAS Scores	Baseline, Cycle 3 Day 1 (cycle = 28 days), and End of Treatment Visit (within 5 to 33 days after last dose of treatment, approximately 1 year total)	The 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) visual analogue scale (VAS) scores range from 0 to 100 with a higher number representing a better health status.
Total Number of Adverse Events (AEs)	Approximately 1 year	—
Total Number of Participants With Adverse Events (AEs) Leading to Dose Modifications	Approximately 1 year	—
Progression Free Survival (PFS)	Approximately 1 year	The time from Day 1 to the date of first documentation of disease progression as assessed by the Investigator and by the IRC per RECIST v1.1. or death due to any cause
Total Number of Participants With Serious Adverse Events (SAEs)	Approximately 1 year	—
Total Number of Participants With Adverse Events (AEs) Leading to Death	Approximately 1 year	—
Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t)	Cycle 1 Day 1 and Cycle 2 Day 1	—
Average AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)	Cycle 2 Day 1	—
Average Time to Maximum Concentration (Tmax)	Cycle 1 Day 1 and Cycle 2 Day 1	—
Average Maximum Concentration (Cmax)	Cycle 1 Day 1 and Cycle 2 Day 1	—
Average Trough Concentration (Ctrough)	Cycle 2 Day 1	—
Average Plasma 2-hydroxyglutarate (2-HG) Concentrations	Cycle 1 Day 1 and Cycle 2 Day 1	—
Number of Participants With no Change, Plus 1 or Plus 2 Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (ECOG PS) Score	Approximately 1 year	From baseline to worst value of post-baseline assessments. ECOG PS scores range from 0 to 5 with 0 representing a person being fully active and 5 being the patient is dead.
Total Number of Participants With Adverse Events (AEs) Leading to Discontinuation	Approximately 1 year	—

Countries

Japan

Participant flow

Participants by arm

Arm	Count
Open-Label Ivosidenib 250 mg Tablets Ivosidenib: Subjects will take 2 tablets (500 mg total) orally once daily.	12
Total	12

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Death	4
Overall Study	Participants still on-study	8

Baseline characteristics

Characteristic	Open-Label Ivosidenib
Age, Continuous	61.5 years STANDARD_DEVIATION 12.27
Age, Customized 45-<65 years old	7 Participants
Age, Customized >=65 years old	5 Participants
Body Mass Index (BMI)	23.1 kg/m^2 STANDARD_DEVIATION 4.39
Race/Ethnicity, Customized Asian	12 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	12 Participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	7 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	4 / 12
other Total, other adverse events	9 / 12
serious Total, serious adverse events	2 / 12

Outcome results

Primary

6-month Progression Free Survival (PFS) Rate

Proportion of subjects who are alive and progression-free (using RECIST v1.1) at 6 months after Day 1 (C1D1) per Independent Radiology Center (IRC)

Time frame: Through 6 months after the first dose

Arm	Measure	Value (NUMBER)
Open-Label Ivosidenib	6-month Progression Free Survival (PFS) Rate	25.0 percentage of participants

Secondary

Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t)

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant was excluded from Cycle 2 Day 1 data analysis since their dose was reduced.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Open-Label Ivosidenib	Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t)	Cycle 1 Day 1	18699 ng*h/mL	Geometric Coefficient of Variation 43.5
Open-Label Ivosidenib	Average Area Under the Concentration-vs Time Curve From 0 to Time of Last Measurable Concentration (AUC0-t)	Cycle 2 Day 1	22404 ng*h/mL	Geometric Coefficient of Variation 27.4

Secondary

Average AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)

Time frame: Cycle 2 Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Open-Label Ivosidenib	Average AUC Over 1 Dosing Interval at Steady State (AUCtau,ss)	74121 ng*h/mL	Geometric Coefficient of Variation 30

Secondary

Average EQ-5D-5L VAS Scores

The 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) visual analogue scale (VAS) scores range from 0 to 100 with a higher number representing a better health status.

Time frame: Baseline, Cycle 3 Day 1 (cycle = 28 days), and End of Treatment Visit (within 5 to 33 days after last dose of treatment, approximately 1 year total)

Population: The number analyzed differs due to missing participant data.

Arm	Measure	Group	Value (MEAN)	Dispersion
Open-Label Ivosidenib	Average EQ-5D-5L VAS Scores	Baseline	78.8 score on a scale	Standard Deviation 10.8
Open-Label Ivosidenib	Average EQ-5D-5L VAS Scores	Cycle 3 Day 1	75.8 score on a scale	Standard Deviation 15.61
Open-Label Ivosidenib	Average EQ-5D-5L VAS Scores	End of Treatment	61.7 score on a scale	Standard Deviation 27.05

Secondary

Average Maximum Concentration (Cmax)

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant's data was excluded from Cycle 2 Day 1 since the ivosidenib dose was reduced.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Open-Label Ivosidenib	Average Maximum Concentration (Cmax)	Cycle 1 Day 1	4918 ng/mL	Geometric Coefficient of Variation 42.7
Open-Label Ivosidenib	Average Maximum Concentration (Cmax)	Cycle 2 Day 1	4781 ng/mL	Geometric Coefficient of Variation 22.8

Secondary

Average Plasma 2-hydroxyglutarate (2-HG) Concentrations

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant's data was excluded from Cycle 2 Day 1 since the ivosidenib dose was reduced.

Arm	Measure	Group	Value (MEAN)	Dispersion
Open-Label Ivosidenib	Average Plasma 2-hydroxyglutarate (2-HG) Concentrations	Cycle 1 Day 1	597 ng/mL	Standard Deviation 532.07
Open-Label Ivosidenib	Average Plasma 2-hydroxyglutarate (2-HG) Concentrations	Cycle 2 Day 1	79.95 ng/mL	Standard Deviation 41.166

Secondary

Average Time to Maximum Concentration (Tmax)

Time frame: Cycle 1 Day 1 and Cycle 2 Day 1

Population: One participant's data was excluded from Cycle 2 Day 1 since the ivosidenib dose was reduced.

Arm	Measure	Group	Value (MEDIAN)
Open-Label Ivosidenib	Average Time to Maximum Concentration (Tmax)	Cycle 1 Day 1	2.98 hours
Open-Label Ivosidenib	Average Time to Maximum Concentration (Tmax)	Cycle 2 Day 1	3.83 hours

Secondary

Average Trough Concentration (Ctrough)

Time frame: Cycle 2 Day 1

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Open-Label Ivosidenib	Average Trough Concentration (Ctrough)	2058 ng/mL	Geometric Coefficient of Variation 28.7

Secondary

Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-BIL21 Questionnaire Scores.

The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (EORTC-QLQ-BIL21) scores range from 0 - 100 with higher scores representing more severe symptoms.

Time frame: Baseline and 1 year

Arm	Measure	Value (MEAN)	Dispersion
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-BIL21 Questionnaire Scores.	8.3 score on a scale	Standard Deviation 12.5

Secondary

Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.

The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30) is comprised of 5 functional scales ((Physical functioning, Role functioning, Cognitive functioning, Emotional functioning and Social functioning), 3 symptom scales (Fatigue, Pain and Nausea/Vomiting), 6 additional single items (Dyspnoea, Insomnia, Appetite Loss, Constipation, Diarrhoea and Financial Difficulties) and global health status (GHS). All of the scale scores range from 0 - 100; for the functional scales and GHS the higher score represents better functioning and for the symptom scales and single items the higher score represents an increase in symptoms. .

Time frame: Baseline and 1 year

Arm	Measure	Group	Value (MEAN)	Dispersion
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Physical Functioning	-6.7 score on a scale	Standard Deviation 15.63
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Role Functioning	-9.3 score on a scale	Standard Deviation 16.9
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Cognitive Functioning	-1.9 score on a scale	Standard Deviation 10.02
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Emotional Functioning	-8.3 score on a scale	Standard Deviation 18.63
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Social Functioning	-14.8 score on a scale	Standard Deviation 17.57
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Fatigue	7.4 score on a scale	Standard Deviation 16.67
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Pain	7.4 score on a scale	Standard Deviation 32.39
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Nausea/Vomiting	7.4 score on a scale	Standard Deviation 12.11
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Dyspnea	22.2 score on a scale	Standard Deviation 40.82
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Insomnia	18.5 score on a scale	Standard Deviation 29.4
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Appetite Loss	7.4 score on a scale	Standard Deviation 32.39
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Constipation	-7.4 score on a scale	Standard Deviation 14.7
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Diarrhea	3.7 score on a scale	Standard Deviation 20.03
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	Financial Difficulties	0.0 score on a scale	Standard Deviation 23.57
Open-Label Ivosidenib	Change From Baseline in Health-Related Quality of Life Using EORTC-QLQ-C30 Questionnaire Scores.	GHS	-20.4 score on a scale	Standard Deviation 22.48

Secondary

Duration of Response (DOR)

The time from date of first documented confirmed complete response (CR) or confirmed partial response (PR) to date of first documented disease progression or death due to any cause