Back to resultsA Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Primary Purpose
Cholangiocarcinoma Non-resectable, Cholangiocarcinoma Metastatic
Status
Not yet recruiting
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
Ivosidenib
Sponsored by
About this trial
This is an interventional treatment trial for Cholangiocarcinoma Non-resectable focused on measuring IDH-1 Mutation, Cholangiocarcinoma Non-resectable with an IDH-1 Mutation, Cholangiocarcinoma Metastatic with an IDH-1 Mutation
Eligibility Criteria
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)
Sites / Locations
- Kanagawa Cancer Center
- Kumamoto University Hospital
- National Hospital Organization Shikoku Cancer Center
- Osaka International Cancer Institute
- Hokkaido University Hospital
- National Cancer Center Hospital
- JPN-002
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Open-Label Ivosidenib
Arm Description
250 mg Tablets
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Progression Free Survival (PFS)
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
Overall Survival (OS)
Objective Response (OR) rate
Complete response or partial response
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
Time to Response (TTR)
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.
The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30) scores range from 0 - 100 and asses both functional scores and symptom scores; for the functional score the higher score represents better functioning and for the symptom scores the higher score represents an increase in symptoms.
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.
Average EQ-5D-5L scores
The 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) scores range from 5 to 25 with a higher number representing a worse health status.
Total Number of Adverse Events (AEs)
Total Number of Adverse Events (AEs) leading to dose modifications
Total Number of Adverse Events (AEs) leading to discontinuation
Total Number of Serious Adverse Events (SAEs)
Total Number of Adverse Events (AEs) leading to death
Average area under the concentration-vs time curve from 0 to time of last measurable concentration (AUC0-t)
Average AUC over 1 dosing interval at steady state (AUCtau,ss)
Average time to maximum concentration (Tmax)
Average maximum concentration (Cmax)
Average trough concentration (Ctrough)
Average plasma 2-hydroxyglutarate (2-HG) concentrations
Change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS)
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT06081829
Brief Title
A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
May 2027 (Anticipated)
Study Completion Date
May 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Servier
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cholangiocarcinoma Non-resectable, Cholangiocarcinoma Metastatic
Keywords
IDH-1 Mutation, Cholangiocarcinoma Non-resectable with an IDH-1 Mutation, Cholangiocarcinoma Metastatic with an IDH-1 Mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Open-Label Ivosidenib
Arm Type
Experimental
Arm Description
250 mg Tablets
Intervention Type
Drug
Intervention Name(s)
Ivosidenib
Intervention Description
Subjects will take 2 tablets (500 mg total) orally once daily.
Primary Outcome Measure Information:
Title
6-month Progression Free Survival (PFS) rate
Description
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
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS)
Description
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
Time Frame
Through 2 years after the last subject was enrolled
Title
Overall Survival (OS)
Time Frame
Through 2 years after the last subject was enrolled
Title
Objective Response (OR) rate
Description
Complete response or partial response
Time Frame
Through 2 years after the last subject was enrolled
Title
Duration of Response (DOR)
Description
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 Frame
Through 2 years after the last subject was enrolled
Title
Time to Response (TTR)
Description
The time from Day 1 to date of first documented confirmed complete response (CR) or confirmed partial response (PR)
Time Frame
Through 2 years after the last subject was enrolled
Title
Change from baseline in Health-Related Quality of Life using EORTC-QLQ-C30 questionnaire scores.
Description
The European Organisation for Research and Treatment of Cancer - Quality Of Life Questionnaire - Core Questionnaire (EORTC-QLQ-C30) scores range from 0 - 100 and asses both functional scores and symptom scores; for the functional score the higher score represents better functioning and for the symptom scores the higher score represents an increase in symptoms.
Time Frame
Through 2 years after the last subject was enrolled
Title
Change from baseline in Health-Related Quality of Life using EORTC-QLQ-BIL21 questionnaire scores.
Description
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
Through 2 years after the last subject was enrolled
Title
Average EQ-5D-5L scores
Description
The 5-level EuroQol five dimensions questionnaire (EQ-5D-5L) scores range from 5 to 25 with a higher number representing a worse health status.
Time Frame
Through the End of Treatment Visit (within 5 to 33 days after last dose of treatment)
Title
Total Number of Adverse Events (AEs)
Time Frame
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Title
Total Number of Adverse Events (AEs) leading to dose modifications
Time Frame
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Title
Total Number of Adverse Events (AEs) leading to discontinuation
Time Frame
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Title
Total Number of Serious Adverse Events (SAEs)
Time Frame
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Title
Total Number of Adverse Events (AEs) leading to death
Time Frame
Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
Title
Average area under the concentration-vs time curve from 0 to time of last measurable concentration (AUC0-t)
Time Frame
Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment (within 33 days of last dose)
Title
Average AUC over 1 dosing interval at steady state (AUCtau,ss)
Time Frame
Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1
Title
Average time to maximum concentration (Tmax)
Time Frame
Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment (within 33 days of last dose)
Title
Average maximum concentration (Cmax)
Time Frame
Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment (within 33 days of last dose)
Title
Average trough concentration (Ctrough)
Time Frame
Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment (within 33 days of last dose)
Title
Average plasma 2-hydroxyglutarate (2-HG) concentrations
Time Frame
Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1, End of Treatment (within 33 days of last dose)
Title
Change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS)
Description
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.
Time Frame
Through the End of Treatment Visit (occurring 28 - 33 days after the last dose)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Institut de Recherches Internationales Servier
Phone
+33 1 55 72 60 00
Email
scientificinformation@servier.com
Facility Information:
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Kumamoto University Hospital
City
Honjō
State/Province
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
National Hospital Organization Shikoku Cancer Center
City
Ko
State/Province
Matsuyama
ZIP/Postal Code
791-0280
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Chuo Ku
State/Province
Osaka
ZIP/Postal Code
541-8567
Country
Japan
Facility Name
Hokkaido University Hospital
City
Kita
State/Province
Sapporo Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
National Cancer Center Hospital
City
Tsukiji
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
JPN-002
City
Chiba
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
http://clinicaltrials.servier.com/
Learn more about this trial
A Phase 2 Study of Ivosidenib in Previously Treated Japanese Subjects With Nonresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
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