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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06501625




Registration number
NCT06501625
Ethics application status
Date submitted
9/07/2024
Date registered
15/07/2024

Titles & IDs
Public title
Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Scientific title
A Phase 1b/2, Safety Lead-in and Dose-Expansion, Open Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Activity of Ivosidenib in Combination With Durvalumab and Gemcitabine/Cisplatin as First-line Therapy in Participants With Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Secondary ID [1] 0 0
2024-514261-19-00
Secondary ID [2] 0 0
S095031-210
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation 0 0
Condition category
Condition code
Cancer 0 0 0 0
Biliary tree (gall bladder and bile duct)
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ivosidenib
Treatment: Drugs - Durvalumab (for the first 8, 21-day, cycles)
Treatment: Drugs - Gemcitabine (for the first 8, 21-day, cycles)
Treatment: Drugs - Cisplatin (for the first 8, 21-day, cycles)
Treatment: Drugs - Durvalumab (starting from cycle 9)
Treatment: Drugs - Ivosidenib Recommended Combination Dose (RCD)

Experimental: Safety Lead-In Phase -

Experimental: Expansion Phase -


Treatment: Drugs: Ivosidenib
Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration

Treatment: Drugs: Durvalumab (for the first 8, 21-day, cycles)
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 8 (21-day) cycles

Treatment: Drugs: Gemcitabine (for the first 8, 21-day, cycles)
1000 mg/m2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

Treatment: Drugs: Cisplatin (for the first 8, 21-day, cycles)
25 mg/m\^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles

Treatment: Drugs: Durvalumab (starting from cycle 9)
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.

Treatment: Drugs: Ivosidenib Recommended Combination Dose (RCD)
RCD administered orally once daily, taken continuously throughout treatment duration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Lead-in Phase: Number of Dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Through Cycle 1 (Cycle 1 is 21 days)
Primary outcome [2] 0 0
Safety Lead-in Phase: Number of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs)
Timepoint [2] 0 0
Through 90 days after the end of treatment (Approximately 5 years)
Primary outcome [3] 0 0
Expansion Phase: Objective response rate (ORR)
Timepoint [3] 0 0
Through the end of the study (Approximately 5 years)
Secondary outcome [1] 0 0
Safety Lead-in Phase: Ivosidenib Area under the concentration-versus-time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t)
Timepoint [1] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [2] 0 0
Safety Lead-in Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss)
Timepoint [2] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [3] 0 0
Safety Lead-in Phase: Ivosidenib time to maximum concentration (Tmax)
Timepoint [3] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [4] 0 0
Safety Lead-in Phase: Ivosidenib maximum concentration (Cmax)
Timepoint [4] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [5] 0 0
Safety Lead-in Phase: Ivosidenib trough concentration (Ctrough)
Timepoint [5] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [6] 0 0
Safety Lead-in Phase: Ivosidenib apparent volume of distribution (Vd/F)
Timepoint [6] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [7] 0 0
Safety Lead-in Phase: Ivosidenib apparent clearance (CL/F)
Timepoint [7] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [8] 0 0
Safety Lead-in Phase: Plasma 2-hydroxygluturate (2-HG) concentrations
Timepoint [8] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [9] 0 0
Expansion Phase: Number of AEs, AESIs, and SAEs
Timepoint [9] 0 0
Through 90 days after the end of treatment (Approximately 5 years)
Secondary outcome [10] 0 0
Expansion Phase: Overall survival (OS)
Timepoint [10] 0 0
Through the end of the study (Approximately 5 years)
Secondary outcome [11] 0 0
Expansion Phase: Duration of response (DOR)
Timepoint [11] 0 0
Through the end of the study (Approximately 5 years)
Secondary outcome [12] 0 0
Expansion Phase: Progression-free survival (PFS)
Timepoint [12] 0 0
Through the end of the study (Approximately 5 years)
Secondary outcome [13] 0 0
Expansion Phase: Disease control
Timepoint [13] 0 0
Through the end of the study (Approximately 5 years)
Secondary outcome [14] 0 0
Expansion Phase: Time to response (TTR)
Timepoint [14] 0 0
Through the end of the study (Approximately 5 years)
Secondary outcome [15] 0 0
Expansion Phase: Ivosidenib Area under the concentration-versus-time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t)
Timepoint [15] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [16] 0 0
Expansion Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss)
Timepoint [16] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [17] 0 0
Expansion Phase: Ivosidenib time to maximum concentration (Tmax)
Timepoint [17] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [18] 0 0
Expansion Phase: Ivosidenib maximum concentration (Cmax)
Timepoint [18] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [19] 0 0
Expansion Phase: Ivosidenib trough concentration (Ctrough)
Timepoint [19] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [20] 0 0
Expansion Phase: Ivosidenib apparent volume of distribution (Vd/F)
Timepoint [20] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [21] 0 0
Expansion Phase: Ivosidenib apparent clearance (CL/F)
Timepoint [21] 0 0
Through the end of treatment (Approximately 5 years)
Secondary outcome [22] 0 0
Expansion Phase: Plasma 2-hydroxygluturate (2-HG) concentrations
Timepoint [22] 0 0
Through the end of treatment (Approximately 5 years)

Eligibility
Key inclusion criteria
* Have a histopathological confirmed diagnosis consistent with locally advanced unresectable or metastatic cholangiocarcinoma.
* Have documented IDH1 gene-mutated cholangiocarcinoma based on local or central laboratory testing (R132C/L/G/H/S mutation variants tested).
* Have at least one evaluable and measurable lesion as defined by RECIST v1.1.
* Have adequate bone marrow function as evidenced by:
* Absolute neutrophil count = 1,500/mm3 or 1.5 ×109/L
* Hemoglobin = 9 g/dL
* Platelet count = 100,000/mm3 or 100 × 109/L
* Have adequate hepatic function as evidenced by:
* Serum bilirubin = 2.0 × the upper limit of normal (ULN); this will not apply to patients with confirmed Gilbert's syndrome. Any clinically significant biliary obstruction should be resolved before randomization
* Aspartate aminotransferase (AST), and alanine aminotransferase (ALT) = 2.5 × ULN; for patients with hepatic metastases, ALT and AST = 5.0 × ULN
* Have adequate renal function, defined as: creatinine clearance > 60 mL/min per 24 hour urine or as calculated on the Cockcroft-Gault formula (using actual body weight):

Creatine CL (mL/min)= (140 - Age) × (weight in kg) × (0.85 if female)/72 × serum creatinine (mg/dL)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Received treatment for locally advanced, unresectable or metastatic disease with the following exceptions:
* Treatment with up to one cycle of durvalumab plus gemcitabine/cisplatin treatment is permitted before study participation. Note: For the Safety Lead-In Phase, participants who received one prior cycle of durvalumab plus gemcitabine/cisplatin and required dose modifications for treatment-related toxicity are excluded.
* Patients who developed recurrent disease > 6 months after surgery with curative intent, and, if given, > 6 months after the completion of adjuvant (chemotherapy and/or radiation).
* Prior exposure to immune-mediated therapy, including, but not limited to, anti-PD-1or other anti-PD-L1, and anti-PD-L2, anti-CTLA-4 antibodies, excluding therapeutic anticancer vaccines.
* Unresolved Grade =2 adverse events from a previous anticancer therapy, with the exception of alopecia and vitiligo and the laboratory values listed in the inclusion criteria.
* Patients with Grade =2 neuropathy to be evaluated on a case-by-case basis after consultation with the medical monitor
* Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with ivosidenib may be included only after consultation with the medical monitor
* Participation in another interventional study at the same time or within 14 days prior to the first study medication (triple combination treatment) administration. For patients having participated to another prior interventional study, the first dose of ivosidenib should occur after a period greater than or equal to 5 half-lives or 28 days, whichever is shorter of the last dose of the prior investigational product.
* Active or prior documented autoimmune or inflammatory disorders including:
* inflammatory bowel disease (e.g., colitis or Crohn's disease)
* diverticulitis (with the exception of diverticulosis)
* systemic lupus erythematosus
* Sarcoidosis syndrome
* Wegener syndrome (granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.)

Note: in cases with no active disease for = 5 years, patients may be considered for inclusion if approved by the Medical Monitor. Participants with the following conditions are eligible for the study:

* chronic skin condition that does not require systemic therapy
* vitiligo
* alopecia
* hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement therapy
* unmedicated celiac disease that is controlled by diet
* Have heart rate-corrected QT interval using Fridericia's formula (QTcF) of = 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome/sudden death, polymorphic ventricular arrhythmia). The Sponsor should review participants with bundle branch block and prolonged QTcF for potential inclusion.
* Have an active infection, including:
* Hepatitis B (clinical evaluation includes: presence of hepatitis B surface antigen [HBsAg] and/or anti-HBcAb with detectable hepatitis B virus [HBV] DNA = 10 IU/mL)
* Hepatitis C
* Tuberculosis (clinical evaluation includes: clinical history, physical examination and/or radiographic findings, and tuberculosis testing as per local practice)
* Human immunodeficiency virus (clinical evaluation includes: positive HIV 1/2 antibodies) Note: Patients with a resolved or past HBV infection (i.e., presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) do not need to be excluded from the study. Patients positive for hepatitis C (HCV) antibody are eligible only if the polymerase chain reaction is negative for HCV RNA.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
16/12/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/01/2030
Actual
Sample size
Target
52
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
Belo Horizonte

Funding & Sponsors
Primary sponsor type
Other
Name
Institut de Recherches Internationales Servier
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies:

* Used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
* Where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.

In addition, access can be requested for all interventional clinical studies in patients:

* sponsored by Servier
* with a first patient enrolled as of 1 January 2004 onwards
* for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
After Marketing Authorization in EEA or US if the study is used for the approval.
Available to whom?
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://clinicaltrials.servier.com/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT06501625