Clinical trial NCT06081829: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Cholangiocarcinoma Non-resectable
Cholangiocarcinoma Metastatic
Keywords: IDH-1 Mutation
Cholangiocarcinoma Non-resectable with an IDH-1 Mutation
Cholangiocarcinoma Metastatic with an IDH-1 Mutation
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2023-10-13
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: 6-month Progression Free Survival (PFS) rate
timeFrame: Through 6 months after the first dose
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Through 2 years after the last subject was enrolled
measure: Overall Survival (OS)
timeFrame: Through 2 years after the last subject was enrolled
measure: Objective Response (OR) rate
timeFrame: Through 2 years after the last subject was enrolled
measure: Duration of Response (DOR)
timeFrame: Through 2 years after the last subject was enrolled
measure: Time to Response (TTR)
timeFrame: Through 2 years after the last subject was enrolled
measure: Change from baseline in Health-Related Quality of Life using EORTC-QLQ-C30 questionnaire scores.
timeFrame: Through 2 years after the last subject was enrolled
measure: Change from baseline in Health-Related Quality of Life using EORTC-QLQ-BIL21 questionnaire scores.
timeFrame: Through 2 years after the last subject was enrolled
measure: Average EQ-5D-5L scores
timeFrame: Through the End of Treatment Visit (within 5 to 33 days after last dose of treatment)
measure: Total Number of Adverse Events (AEs)
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Total Number of Adverse Events (AEs) leading to dose modifications
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Total Number of Adverse Events (AEs) leading to discontinuation
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Total Number of Serious Adverse Events (SAEs)
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Total Number of Adverse Events (AEs) leading to death
timeFrame: Through the Safety Follow-up Visit (28-33 days after discontinuation of treatment)
measure: Average area under the concentration-vs time curve from 0 to time of last measurable concentration (AUC0-t)
timeFrame: 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)
measure: Average AUC over 1 dosing interval at steady state (AUCtau,ss)
timeFrame: Each cycle is 28 days: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 3 Day 1
measure: Average time to maximum concentration (Tmax)
timeFrame: 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)
measure: Average maximum concentration (Cmax)
timeFrame: 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)
measure: Average trough concentration (Ctrough)
timeFrame: 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)
measure: Average plasma 2-hydroxyglutarate (2-HG) concentrations
timeFrame: 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)
measure: Change from baseline in Eastern Cooperative Oncology Group (ECOG) performance status (ECOG PS)
timeFrame: Through the End of Treatment Visit (occurring 28 - 33 days after the last dose)
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East (JPN-002)
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital (JPN-004)
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center (JPN-007)
city: Osaka
country: Japan
facility: Osaka International Cancer Institute (JPN-005)
city: Sapporo
country: Japan
facility: Hokkaido University Hospital (JPN-006)
city: Tokyo
country: Japan
facility: National Cancer Center Hospital (JPN-001)
city: Yokohama
country: Japan
facility: Kanagawa Cancer Center (JPN-003)
Study officials:
References: