NCT05615818

Personalized Medicine for Advanced Biliary Cancer Patients

Molecular Targeted Maintenance Therapy Versus Standard of Care in Advanced Biliary Cancer: an International, Randomised, Controlled, Open-label, Platform Phase 3 Trial

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 800 (estimated)
• Sponsor: UNICANCER · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The object of this trial is to evaluate whether the introduction of a targeted therapy after 4 cycles of the current standard-of-care treatment for advanced biliary cancer is superior to continuing with the standard treatment. The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a molecular profile of the patient's tumour will be obtained, and (ii) a randomised comparative trial in which patients with disease control after 4 cycles of standard treatment, and whose tumour harbours a targetable molecular alteration, will be randomised (2:1) to receive either a matched targeted therapy or to continue with the standard treatment.

Detailed description

This is a Phase 3, multicentre, randomised, open-label trial to evaluate whether the introduction of molecular targeted therapy (MTT) as maintenance after 4 cycles of standard-of-care first-line systemic therapy (1L SoC) is superior to continuation of 1L-SoC in the treatment of patients with ABC. The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, and (ii) a randomised comparative trial. The aim of the screening phase is to identify a medically suitable population, to obtain a molecular profile of the patient's tumour, to collect baseline data concerning patient demographics and disease characteristics and to obtain pre-treatment blood and tumour samples for further translational research. A genetic profile will be obtained from tumour-derived DNA and RNA samples by next-generation sequencing and from circulating tumour DNA. The trial Molecular Tumour Board will determine whether each patient harbours a targetable molecular alteration for one or more of the trial MTTs. Patients with disease control after 4 cycles of 1L-SoC, who did not experience limiting toxicity, and whose tumour harbours at least one targetable molecular alteration, will be invited to participate in the randomised phase of the trial in which 159 eligible patients will be randomised (2:1) to receive either maintenance therapy with a matched MTT or to continue 1L-SoC treatment.

Conditions

• Biliary Tract Neoplasms

Interventions

Type	Name	Description
DRUG	Futibatinib	Dose 20 mg once a day (QD)
DRUG	Ivosidenib	Dose 500 mg QD
DRUG	Zanidatamab	Dose: Patients \< 70 kg: 1800 mg every 3 weeks (Q3W), Patients ≥ 70 kg: 2400 mg Q3W
DRUG	Trastuzumab	Loading dose 8 mg/kg, then 6 mg/kg Q3W (Combination with neratinib)
DRUG	Neratinib	Dose: 240 mg QD (combination with trastuzumab)
DRUG	Encorafenib	Dose: 450 mg QD (Combination with binimetinib)
DRUG	Binimetinib	Dose: 45 mg twice a day (BID) (Combination with encorafenib)
DRUG	Niraparib	Dose: 200 mg QD or 300 mg QD
DRUG	Cisplatin	Dose: 25 mg/m2 IV on days 1 and 8 Q3W (CISGEM)
DRUG	Gemcitabine	Dose: 1000 mg/m2 IV on days 1 and 8 Q3W (CISGEM)

Timeline

• Start date: 2024-07-18
• Primary completion: 2027-06-01
• Completion: 2028-06-01
• First posted: 2022-11-14
• Last updated: 2025-04-23

Locations

69 sites across 3 countries: Belgium, France, United Kingdom