An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
- Registration Number
- NCT05876754
- Lead Sponsor
- Servier Affaires Médicales
- Brief Summary
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.
- Detailed Description
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 If at any point ivosidenib is made available as a medical prescription at the patient's site, patients will be withdrawn from the study treatment and patients will be followed to collect data on overall survival.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
- Diagnosis of nonresectable or metastatic Cholangiocarcinoma (CCA), not eligible for curative-intent resection, transplantation, or ablative therapies
- Have a documented IDH1 R132C, R132L, R132G, R132H, or R132S gene-mutated disease
- Have tried at least 1 prior type of systemic therapy for CCA, and have recovered from any side effects
- Female patients of childbearing potential must have a negative blood pregnancy test prior to starting treatment and must agree to use 2 forms of contraception from the time they enroll to 1 month after their last dose of study drug
- Male patients with a female partner with childbearing potential must also agree to use 2 forms of contraception from the time they enroll to 1 month after their last dose of study drug
- Received a prior IDH1 inhibitor
- Have received a transplant
- Have received systemic cancer treatment or radiotherapy within 2 weeks prior to Day 1 of Cycle 1
- Have received hepatic radiation, chemoembolization, and radiofrequency ablation within 4 weeks prior to Day 1 of Cycle 1
- Have ongoing brain metastases requiring steroids
- Have underwent major surgery within 4 weeks of Day 1 of Cycle 1 prior to C1D1
- Have an active hepatitis B (HBV) or hepatitis C (HCV) infections, known positive human immunodeficiency virus (HIV) antibody results, or acquired immunodeficiency syndrome (AIDS) related illness
- Are pregnant or breastfeeding
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ivosidenib Ivosidenib Oral Tablet Ivosidenib 500 mg, taken orally as two 250 mg tablets once daily for an unlimited amount of continuous 28-day cycles
- Primary Outcome Measures
Name Time Method Change from baseline to the worst on-treatment value of laboratory abnormalities. Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment 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.
Number of patients with vital sign values outside limits of the normal range at each time point. Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment Vital signs include systolic and diastolic blood pressure, heart rate, respiratory rate, and temperature.
Mean change from baseline values to the worst on-treatment value of patients with vital signs outside limits of the normal range Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment 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.
Number of Adverse Events (AEs) from Day 1 of Cycle 1 through 28 days after last study treatment Day 1 of cycle 1, Day 1 of each consecutive cycle, 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.
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 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 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.
Change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score from baseline to worst value out of the post-baseline assessments. Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment 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.
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). 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 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.
Number of Adverse Events (AEs) leading to discontinuation or death from day 1 through 28 days after the last study treatment Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after 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.
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. Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment 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.
- Secondary Outcome Measures
Name Time Method Progression-free survival (PFS) time beginning at enrollement through 28 days after last treatment 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.
Overall survival (OS) through 28 days after last treatment 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.
Change from baseline of Quality of life scores through 28 days after last study treatment 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.
Proportion of days at home or hospital for all patients 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). through 28 days after last treatment 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.
Duration of response (DOR) through 28 days after last treatment 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 to response (TTR) through 28 days after last treatment 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.
Trial Locations
- Locations (78)
Medizinische Fakultaet der Universitaet Freiburg
🇩🇪Freiburg, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Klinikum der Universitaet Muenchen-Grosshadern
🇩🇪München, Germany
Hospital Universitario Reina Sofa
🇪🇸Córdoba, Spain
Hospital General de Elche
🇪🇸Elche, Spain
National Center of Oncology of Ra M
🇦🇲Yerevan, Armenia
Universitaetsklinikum Frankfurt
🇩🇪Frankfurt, Germany
Erebouni MC
🇦🇲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
🇦🇺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
Medizinische Universitaet Wien Universitaetsklinik fuer Innere Medizin I
🇦🇹Wien, Austria
Universite Libre de Bruxelles ULB -
🇧🇪Brussel, Belgium
Universitair Ziekenhuis Gent UZ Gent
🇧🇪Gent, Belgium
UZ Leuven
🇧🇪Leuven, Belgium
Cliniques Univ St Luc - Gastro-Enterology
🇧🇪Woluwe-Saint-Lambert, Belgium
Tom Baker Cancer Center
🇨🇦Calgary, Canada
NSHA, QEII Health Sciences Centre
🇨🇦Halifax, Canada
London Regional Cancer Program
🇨🇦London, Canada
Princess Margaret Cancer Center
🇨🇦Toronto, Canada
Sunnybrook Health Sciences Centre
🇨🇦Toronto, Canada
Hôpital Privé Jean Mermoz
🇫🇷Lyon, France
Hopital de la Timone
🇫🇷Marseille, France
CHU Montpellier
🇫🇷Montpellier, France
Centre Hospitalier Universitaire de Nantes CHU de Nantes
🇫🇷Nantes, France
Institute Mutualiste Montsouris
🇫🇷Paris, France
CHU Bordeaux, Hôpital Haut-Lévêque
🇫🇷Pessac, France
CHU de Poitiers
🇫🇷Poitiers, France
Charite Universittsmedizin Berlin
🇩🇪Berlin, Germany
Universitaetsklinikum Carl-Gustav-Carus
🇩🇪Dresden, Germany
Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
🇩🇪Düsseldorf, Germany
Cork University Hospital
🇮🇪Cork, Ireland
St. James Hospital
🇮🇪Dublin, Ireland
St. Vincent's Private Hospital
🇮🇪Dublin, Ireland
Policlinico S. Orsola-Malpighi
🇮🇹Bologna, Italy
AOU Careggi
🇮🇹Florence, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Istituto Nazionale Tumori IRCCS Fondazione Pascale
🇮🇹Napoli, Italy
IRCCS Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
🇮🇹Roma, Italy
Humanitas Research Hospital
🇮🇹Rozzano, Italy
Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Casa Sollievo della Sofferenza (CSS)
🇮🇹San Giovanni Rotondo, Italy
A.O.U. Città della Salute e della Scienza di Torino
🇮🇹Turin, Italy
AOUI Verona - Ospedale Borgo Roma
🇮🇹Verona, Italy
CHA Bundang Medical Center
🇰🇷Seongnam, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University
🇰🇷Seoul, Korea, Republic of
Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Amsterdam UMC, location AMC
🇳🇱Amsterdam, Netherlands
Universiteit Maastricht UM - Maastricht University Medical Centre MUMC
🇳🇱Limburg, Netherlands
Institutul Clinic Fundeni
🇷🇴Bucarest, Romania
Regional Institute of Gastroenterology and Hepatology
🇷🇴Cluj-Napoca, Romania
Centrul de Oncologie Sfantu Necta
🇷🇴Craiova, Romania
Radiotherapy Center Cluj
🇷🇴Otopeni, Romania
Municipal Hospital Ploiesti
🇷🇴Ploiesti, Romania
Complejo Hospitalario Universitario A Coruña (CHUAC)
🇪🇸A Coruña, Spain
Hospital Universitari Vall d'Hebron/Vall Hebron Institute of Oncology (VHIO)
🇪🇸Barcelona, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario 12 de octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Spain
Sahlgrenska University Hospital
🇸🇪Gothenburg, Sweden
Karolinska University Hospital
🇸🇪Stockholm, Sweden
University Hospitals Birmingham (UHB) NHS Foundation Trust - Queen Elizabeth Hospital Birmingham (QEHB)
🇬🇧Birmingham, United Kingdom
The Beatson Institute West of Scotland Cancer Research
🇬🇧Glasgow, United Kingdom
Imperial College London
🇬🇧London, United Kingdom
University College London Hospital NHS Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
The Newcastle Upon Tyne Hospitals
🇬🇧Newcastle Upon Tyne, United Kingdom