An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma

Cholangiocarcinoma Clinical Trial

— ProvIDHe  

Official title:

An Open-Label Early Access Phase 3b Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05876754
• Other study ID #: DIM-95031-002
• Secondary ID: 2022-501463-40
• Status: Recruiting
• Phase: Phase 3
• Start date: May 3, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: June 2024
• Source: Servier
• Contact: Institut de Recherches Internationales Servier, Clinical Studies
• Phone: +33 1 55 72 60 00
• Email: scientificinformation[@]servier.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: June 1, 2025
• Est. primary completion date: June 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Cholangiocarcinoma

Intervention

Drug:
• Ivosidenib Oral Tablet
Ivosidenib 500 mg

Locations

Country	Name	City	State
Armenia	Erebouni MC	Yerevan
Armenia	National Center of Oncology of Ra M	Yerevan
Australia	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
Austria	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
Belgium	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
Canada	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
France	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
Germany	Charite Universittsmedizin Berlin	Berlin
Germany	Universitaetsklinikum Carl-Gustav-Carus	Dresden
Germany	Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitaetsklinikum Frankfurt	Frankfurt
Germany	Medizinische Fakultaet der Universitaet Freiburg	Freiburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Klinikum der Universitaet Muenchen-Grosshadern	München
Ireland	Cork University Hospital	Cork
Ireland	St. James Hospital	Dublin
Ireland	St. Vincent's Private Hospital	Dublin
Italy	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
Korea, Republic of	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
Netherlands	Amsterdam UMC, location AMC	Amsterdam
Netherlands	Universiteit Maastricht UM - Maastricht University Medical Centre MUMC	Limburg
Romania	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
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC)	A Coruña
Spain	Hospital Universitari Vall d'Hebron/Vall Hebron Institute of Oncology (VHIO)	Barcelona
Spain	Hospital Universitario Reina Sofa	Córdoba
Spain	Hospital General de Elche	Elche
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
Sweden	Sahlgrenska University Hospital	Gothenburg
Sweden	Karolinska University Hospital	Stockholm
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Servier Affaires Médicales

Countries where clinical trial is conducted

Armenia,  Australia,  Austria,  Belgium,  Canada,  France,  Germany,  Ireland,  Italy,  Korea, Republic of,  Netherlands,  Romania,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
Primary	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.	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
Primary	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.	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
Primary	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.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Primary	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.	Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
Primary	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.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Primary	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.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Primary	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.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Primary	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.	Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Secondary	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.	through 28 days after last treatment
Secondary	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.	through 28 days after last treatment
Secondary	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.	through 28 days after last treatment
Secondary	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.	through 28 days after last treatment
Secondary	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.	through 28 days after last study treatment
Secondary	Proportion of days at home or hospital for all patients		through 28 days after last treatment
Secondary	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.	through 28 days after last treatment