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

Phase 2Active Not RecruitingNCT06081829

Servier12 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cholangiocarcinoma Non-resectable Cholangiocarcinoma Metastatic

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

Time frame: Approximately 1 year

Overall Survival (OS)

Time frame: Approximately 1 year

Objective Response (OR) Rate

Complete response or partial response

Time frame: Approximately 1 year

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 frame: Approximately 1 year

Time to Response (TTR)

The time from Day 1 to date of first documented confirmed complete response (CR) or confirmed partial response (PR)

Time frame: Approximately 1 year

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

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

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)

Total Number of Adverse Events (AEs)

Time frame: Approximately 1 year

Total Number of Participants With Adverse Events (AEs) Leading to Dose Modifications

Time frame: Approximately 1 year

Total Number of Participants With Adverse Events (AEs) Leading to Discontinuation

Time frame: Approximately 1 year

Total Number of Participants With Serious Adverse Events (SAEs)

Time frame: Approximately 1 year

Total Number of Participants With Adverse Events (AEs) Leading to Death

Time frame: Approximately 1 year

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

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

Time frame: Cycle 2 Day 1

Average Time to Maximum Concentration (Tmax)

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

Average Maximum Concentration (Cmax)

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

Average Trough Concentration (Ctrough)

Time frame: Cycle 2 Day 1

Average Plasma 2-hydroxyglutarate (2-HG) Concentrations

Time frame: 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

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: Approximately 1 year

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

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes