Clinical trial NCT05876754: An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
Official title: An Open-Label Early Access Phase 3b Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Cholangiocarcinoma
Keywords: CCA
Pretreated locally advanced or metastatic cholangiocarcinoma
Lead sponsor: Servier
Sponsor class: INDUSTRY
First posted: 2023-05-25
Enrollment: 220
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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Adverse Events (AEs) from Day 1 of Cycle 1 through 28 days after last study treatment
timeFrame: Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
measure: 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).
timeFrame: 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
measure: 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
timeFrame: 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
measure: Change in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score from baseline to worst value out of the post-baseline assessments.
timeFrame: Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
measure: Number of Adverse Events (AEs) leading to discontinuation or death from day 1 through 28 days after the last study treatment
timeFrame: Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 days after last study treatment
measure: 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.
timeFrame: Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
measure: Change from baseline to the worst on-treatment value of laboratory abnormalities.
timeFrame: Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
measure: Number of patients with vital sign values outside limits of the normal range at each time point.
timeFrame: Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
measure: Mean change from baseline values to the worst on-treatment value of patients with vital signs outside limits of the normal range
timeFrame: Screening visit, Day 1 of cycle 1, Day 1 of each consecutive cycle, 28 + 14 days (maximum) after last study treatment
Secondary outcomes:
measure: Progression-free survival (PFS) time beginning at enrollement
timeFrame: through 28 days after last treatment
measure: Overall survival (OS)
timeFrame: through 28 days after last treatment
measure: Duration of response (DOR)
timeFrame: through 28 days after last treatment
measure: Time to response (TTR)
timeFrame: through 28 days after last treatment
measure: Change from baseline of Quality of life scores
timeFrame: through 28 days after last study treatment
measure: Proportion of days at home or hospital for all patients
timeFrame: through 28 days after last treatment
measure: Change from baseline of health economic measures, as assessed by the 5-level EuroQol 5-dimensional questionnaire (EQ-5D-5).
timeFrame: through 28 days after last treatment
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Erebouni MC
city: Yerevan
country: Armenia
facility: National Center of Oncology of Ra M
city: Brisbane
country: Australia
facility: Royal brisbane & Women's Hospital
city: Fitzroy
country: Australia
facility: St Vincent's Hospital
city: Subiaco
country: Australia
facility: St John of God Hospital - Bendat Family Comprehensive Cancer Centre (BFCCC)
city: Sydney
country: Australia
facility: Kinghorn Cancer Centre
city: Woodville
country: Australia
facility: The Queen Elizabeth Hospital
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH
city: Salzburg
country: Austria
facility: Universitaetsklinik fuer Innere Medizin III, mit Hämatologie, internistischer Onkologie, Hämostaseologie, Infektiologie, Rheumatologie und Onkologisches Zentrum
city: Wien
country: Austria
facility: Medizinische Universitaet Wien Universitaetsklinik fuer Innere Medizin I
city: Brussel
country: Belgium
facility: Universite Libre de Bruxelles ULB -
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven
city: Woluwe-Saint-Lambert
country: Belgium
facility: Cliniques Univ St Luc - Gastro-Enterology
city: Calgary
country: Canada
facility: Tom Baker Cancer Center
city: Halifax
country: Canada
facility: NSHA, QEII Health Sciences Centre
city: London
country: Canada
facility: London Regional Cancer Program
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
city: Lyon
country: France
facility: Hôpital Privé Jean Mermoz
city: Marseille
country: France
facility: Hopital de la Timone
city: Montpellier
country: France
facility: CHU Montpellier
city: Nantes
country: France
facility: Centre Hospitalier Universitaire de Nantes CHU de Nantes
city: Paris
country: France
facility: Institute Mutualiste Montsouris
city: Pessac
country: France
facility: CHU Bordeaux, Hôpital Haut-Lévêque
city: Poitiers
country: France
facility: CHU de Poitiers
city: Berlin
country: Germany
facility: Charite Universittsmedizin Berlin
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl-Gustav-Carus
city: Düsseldorf
country: Germany
facility: Klinik für Gastroenterologie, Hepatologie und Infektiologie Universitätsklinikum Düsseldorf
city: Frankfurt
country: Germany
facility: Universitaetsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Medizinische Fakultaet der Universitaet Freiburg
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: München
country: Germany
facility: Klinikum der Universitaet Muenchen-Grosshadern
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: St. James Hospital
city: Dublin
country: Ireland
facility: St. Vincent's Private Hospital
city: Bologna
country: Italy
facility: Policlinico S. Orsola-Malpighi
city: Florence
country: Italy
facility: AOU Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori IRCCS Fondazione Pascale
city: Reggio Emilia
country: Italy
facility: IRCCS Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
city: Rozzano
country: Italy
facility: Humanitas Research Hospital
city: San Giovanni Rotondo
country: Italy
facility: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) - Ospedale Casa Sollievo della Sofferenza (CSS)
city: Turin
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino
city: Verona
country: Italy
facility: AOUI Verona - Ospedale Borgo Roma
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location AMC
city: Limburg
country: Netherlands
facility: Universiteit Maastricht UM - Maastricht University Medical Centre MUMC
city: Bucarest
country: Romania
facility: Institutul Clinic Fundeni
city: Cluj-Napoca
country: Romania
facility: Regional Institute of Gastroenterology and Hepatology
city: Craiova
country: Romania
facility: Centrul de Oncologie Sfantu Necta
city: Otopeni
country: Romania
facility: Radiotherapy Center Cluj
city: Ploiesti
country: Romania
facility: Municipal Hospital Ploiesti
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC)
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron/Vall Hebron Institute of Oncology (VHIO)
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofa
city: Elche
country: Spain
facility: Hospital General de Elche
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Pamplona
country: Spain
facility: Hospital Universitario de Navarra
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham (UHB) NHS Foundation Trust - Queen Elizabeth Hospital Birmingham (QEHB)
city: Glasgow
country: United Kingdom
facility: The Beatson Institute West of Scotland Cancer Research
city: London
country: United Kingdom
facility: Imperial College London
city: London
country: United Kingdom
facility: University College London Hospital NHS Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals
Study officials:
References: