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.
Ivosidenib is approved in the United States and in EU for the treatment of advanced or metastatic CCA; this study is being conducted to conslidate the data related to the safety, efficacy, and impact on quality of life for patients. This is an open-label, single-arm study of ivosidenib, which means that all patients meeting eligibility criteria will receive two 250 mg ivosidenib tablets, totaling 500mg of drug, to be taken orally, once daily, for 28 consecutive days, also referred to as one cycle. Additional cycles can continue as long as clinical benefit is confirmed by an investigator, and consent is maintained. There will be a screening visit, study visit on day 1 of each cycle, withdrawal visit within 42 days of stopping treatment, and a follow-up visit every 6 months for up to 18 months after stopping treatment. This results in a minimum of 6 study visits for the completion of one 28-day cycle of ivosidenib. One additional study visit will be added on day one of each additional cycle of treatment. Study visits will include an electrocardiogram (ECG), physical exam, tumor assessment, according to local practive at a given site and blood and urine analyses. If at any point ivosidenib is made available as a medical prescription at the patient's site, patients will be withdrawn from the study treatment and patients will be followed to collect data on overall survival.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
299
Ivosidenib 500 mg
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Progression-free survival (PFS) time beginning at enrollement
PFS is defined as the time from the date of enrollment to the date at which the disease escalates or progresses. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.
Time frame: through 28 days after last treatment
Overall survival (OS)
OS is defined as the time from date of enrollment to the date of death due to any cause. It will be assessed using the Kaplan-Meier (KM) method curves and estimates.
Time frame: through 28 days after last treatment
Duration of response (DOR)
DOR is defined as the time from the date of response to either progression or death. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.
Time frame: through 28 days after last treatment
Time to response (TTR)
TTR is defined as the time from the date of enrollment to the date of response. It will be assessed using the Kaplan-Meier (KM) method curves and estimates. This will be based on tumor assessments conducted by the investigator according to local clinical practice.
Time frame: through 28 days after last treatment
Change from baseline of Quality of life scores
Measured by the validated European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Cholangiocarcinoma and Gallbladder Cancer Module (QLQ-BIL21). EORTC QLQ-BIL21, will be evaluated for patients with a baseline assessment and at least 1 post-baseline QLQ-BIL21 assessment that generates a score. Change from baseline for each time point, will be summarized using descriptive statistics.
Time frame: through 28 days after last study treatment
Proportion of days at home or hospital for all patients
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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
...and 74 more locations
Time frame: through 28 days after last treatment
Change from baseline of health economic measures, as assessed by the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5).
Health economic measures, as assessed by the EQ-5D-5L, will be evaluated for patients with a baseline assessment and at least 1 post-baseline EQ-5D-5L assessment that generate a score. Change from baseline scores for each time point will be quantified with descriptive statistics.
Time frame: through 28 days after last treatment