Ivosidenib Plus Durvalumab and Gemcitabine/Cisplatin as First-Line Therapy in Participants With Locally Advanced or Metastatic Cholangiocarcinoma With an IDH1 Mutation
NCT Number: NCT06501625
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Locally Advanced, Unresectable or Metastatic Cholangiocarcinoma With an IDH1 Mutation
Interventions: DRUG: Ivosidenib|DRUG: Durvalumab (for the first 8, 21-day, cycles)|DRUG: Gemcitabine (for the first 8, 21-day, cycles)|DRUG: Cisplatin (for the first 8, 21-day, cycles)|DRUG: Durvalumab (starting from cycle 9)|DRUG: Ivosidenib Recommended Combination Dose (RCD)
Sponsor: Institut de Recherches Internationales Servier
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 52
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12-16
Completion Date: 2030-01-15

Summary:
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.

Primary Outcome Measures: Safety Lead-in Phase: Number of Dose-limiting toxicities (DLTs), 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), 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, Through the end of the study (Approximately 5 years)
Secondary Outcome Measures: Safety Lead-in Phase: Ivosidenib Area under the concentration-versus-time curve (AUC) from time 0 to time of last measurable concentration (AUC0-t), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Ivosidenib time to maximum concentration (Tmax), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Ivosidenib maximum concentration (Cmax), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Ivosidenib trough concentration (Ctrough), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Ivosidenib apparent volume of distribution (Vd/F), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Ivosidenib apparent clearance (CL/F), Through the end of treatment (Approximately 5 years)|Safety Lead-in Phase: Plasma 2-hydroxygluturate (2-HG) concentrations, Through the end of treatment (Approximately 5 years)|Expansion Phase: Number of AEs, AESIs, and SAEs, Through 90 days after the end of treatment (Approximately 5 years)|Expansion Phase: Overall survival (OS), Through the end of the study (Approximately 5 years)|Expansion Phase: Duration of response (DOR), Through the end of the study (Approximately 5 years)|Expansion Phase: Progression-free survival (PFS), Through the end of the study (Approximately 5 years)|Expansion Phase: Disease control, Confirmed CR, confirmed PR, or stable disease \[SD\], Through the end of the study (Approximately 5 years)|Expansion Phase: Time to response (TTR), 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), Through the end of treatment (Approximately 5 years)|Expansion Phase: Ivosidenib AUC over 1 dosing interval at steady state (AUCtau,ss), Through the end of treatment (Approximately 5 years)|Expansion Phase: Ivosidenib time to maximum concentration (Tmax), Through the end of treatment (Approximately 5 years)|Expansion Phase: Ivosidenib maximum concentration (Cmax), Through the end of treatment (Approximately 5 years)|Expansion Phase: Ivosidenib trough concentration (Ctrough), Through the end of treatment (Approximately 5 years)|Expansion Phase: Ivosidenib apparent volume of distribution (Vd/F), Through the end of treatment (Approximately 5 years)|Expansion Phase: Ivosidenib apparent clearance (CL/F), Through the end of treatment (Approximately 5 years)|Expansion Phase: Plasma 2-hydroxygluturate (2-HG) concentrations, Through the end of treatment (Approximately 5 years)