The objective of this study is to investigate 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. The study will begin with a safety lead-in phase (Phase 1b study) to determine the recommended combination dose (RDC) and then will transition to an expansion phase (Phase 2 study) to assess the clinical activity of ivosidenib in combination with durvalumab and gemcitabine/cisplatin at the RCD. During the treatment period participants will have study visits on days 1, 8, and 15 of Cycle 1, on days 1 and 8 of Cycle 2 to 8, and on day 1 of each additional cycle. Cycles 1 through 8 are 21 day cycles, and each following cycle is 28 days. Approximately 30 days and 90 days after treatment has ended, safety follow-up visits will occur and then participants will be followed for survival every 3 months. Study visits may include blood tests, ECG, vital signs, and a physical examination.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
52
Two 250 mg tablets, totaling 500 mg, administered orally once daily, taken continuously throughout treatment duration
1500mg intravenous (IV) infusion every 3 weeks, for a maximum of 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
25 mg/m\^2 IV infusion on days 1 and 8 of every 21-day cycle, for a maximum of 8 cycles
1500mg intravenous (IV) infusion every 4 weeks, starting from cycle 9. Cycles are 28 days long, starting Cycle 9.
RCD administered orally once daily, taken continuously throughout treatment duration
Usc Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGNorthwestern Medicine
Chicago, Illinois, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGDuke University
Durham, North Carolina, United States
Safety Lead-in Phase: Number of Dose-limiting toxicities (DLTs)
Time frame: Through Cycle 1 (Cycle 1 is 21 days)
Safety Lead-in Phase: Number of adverse events (AEs), adverse events of special interest (AESIs), and serious adverse events (SAEs)
Time frame: Through 90 days after the end of treatment (Approximately 5 years)
Expansion Phase: Objective response rate (ORR)
Confirmed complete response (CR) or confirmed partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Through the end of the study (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib Area under the concentration-versus-time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib time to maximum concentration (Tmax)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib maximum concentration (Cmax)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib trough concentration (Ctrough)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib apparent volume of distribution (Vd/F)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Ivosidenib apparent clearance (CL/F)
Time frame: Through the end of treatment (Approximately 5 years)
Safety Lead-in Phase: Plasma 2-hydroxygluturate (2-HG) concentrations
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Number of AEs, AESIs, and SAEs
Time frame: Through 90 days after the end of treatment (Approximately 5 years)
Expansion Phase: Overall survival (OS)
Time frame: Through the end of the study (Approximately 5 years)
Expansion Phase: Duration of response (DOR)
Time frame: Through the end of the study (Approximately 5 years)
Expansion Phase: Progression-free survival (PFS)
Time frame: Through the end of the study (Approximately 5 years)
Expansion Phase: Disease control
Confirmed CR, confirmed PR, or stable disease \[SD\]
Time frame: Through the end of the study (Approximately 5 years)
Expansion Phase: Time to response (TTR)
Time frame: Through the end of the study (Approximately 5 years)
Expansion Phase: Ivosidenib Area under the concentration-versus-time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Ivosidenib time to maximum concentration (Tmax)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Ivosidenib maximum concentration (Cmax)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Ivosidenib trough concentration (Ctrough)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Ivosidenib apparent volume of distribution (Vd/F)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Ivosidenib apparent clearance (CL/F)
Time frame: Through the end of treatment (Approximately 5 years)
Expansion Phase: Plasma 2-hydroxygluturate (2-HG) concentrations
Time frame: Through the end of treatment (Approximately 5 years)
Institut de Recherches Internationales Servier (I.R.I.S.) Clinical Studies Department
CONTACT
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