Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer

NCT07745296 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: UC-GMP-2601 - PRODIGE 1222025-524960-38-00
• Study Type: interventional
• Target: 990
• Locations: 0 countries
• Sites: N/A

Brief Summary

The objective of SAFIR-IMPACT BTC is to see whether, combining or replacing the standard adjuvant chemotherapy with a targeted therapy matched to the person's cancer, is better than the standard treatment alone in delaying or preventing the return of the cancer. Three different targeted therapies will be evaluated, each of which recognises a different type of abnormality in cancer cells:

• Ivosidenib - a drug which acts on a specific abnormality in a protein called IDH1.
• Futibatinib - a drug which acts on abnormalities in a protein called FGFR2
• Zanidatamab - a drug which acts on cancers that produce more than the usual quantity of a protein called HER2. The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a sample of the patient's tumour will be tested to see if it has one of the target abnormalities being studied (ii) a randomised comparative phase (for selected patients only) which consists of comparing two treatment options: some patients will receive the targeted therapy specific to the abnormality identified in their tumour, while others will receive the standard treatment. Patients will be assigned to one treatment or the other by a random draw: they will have a 2 in 3 chance of receiving the targeted therapy. Randomised participants will:
• Take their assigned treatment for 6 months
• Visit the clinic once every 3 weeks for checkups and tests
• Keep a diary of their symptoms and the treatment they take at home Follow-up information will be collected for all participants until the end of the trial.

Conditions

Biliary Tract Cancer (BTC)

Keywords

Adjuvant; Targeted therapy; ESCAT; Personalised medicine; Cholangiocarcinoma

Outcome Measures

Primary Outcomes (1)

• Relapse-free survival

  Time from randomisation to the first documented relapse of disease, as assessed by the investigator, or death from any cause, whichever occurs first

  From randomisation to disease or death, up to 5 years

Secondary Outcomes (8)

• Overall Survival

  From randomisation to death, up to 5 years

• Post-relapse survival

  From randomisation to death, up to 5 years

• ctDNA-clearance

  From randomisation to 24 weeks

• Time-to-ctDNA recurrence

  From randomisation, up to 5 years

• Incidence of Adverse Events

  From randomisation, up to 5 years

Study Arms (2)

Experimental

EXPERIMENTAL

Molecular targeted therapy matched to genetic alteration carried by the tumour

Drug: Futibatinib; Drug: Ivosidenib + Capecitabine; Drug: Zanidatamab + Capecitabine

Control

ACTIVE COMPARATOR

Standard of care treatment for adjuvant biliary tract cancer

Drug: Capecitabine (Xeloda)

Interventions

Futibatinib DRUG

Dose 20 mg once a day (QD)

Experimental

Ivosidenib + Capecitabine DRUG

Ivosidenib: Dose 500 mg QD Capecitabine: 1250mg/m² BID for 14 days on, 7 days off, in 3 week cycles

Experimental

Zanidatamab + Capecitabine DRUG

Zanidatamab: Patients \< 70 kg: 1800 mg every 3 weeks (Q3W), Patients ≥ 70 kg: 2400 mg Q3W Capecitabine: 1250mg/m² BID for 14 days on, 7 days off, in 3 week cycles

Experimental

Capecitabine (Xeloda) DRUG

1250mg/m² BID for 14 days on, 7 days off, in 3 week cycles

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed a written informed consent form prior to any trial specific procedures (Consent #1)
• Histologically-proven intrahepatic cholangiocarcinoma, perihilar or distal extrahepatic cholangiocarcinoma or gallbladder carcinoma (ampullary carcinoma is excluded)
• Macroscopically complete resection of the primary tumour (R0 or R1 surgical margin status)
• Aged ≥18 years
• Affiliated to a social security system or in possession of equivalent private health insurance (according to local country health provision arrangements).

You may not qualify if:

• Contraindication to standard adjuvant therapy
• Prior anticancer therapy in the neoadjuvant or adjuvant setting.
• Patients with gallbladder cancer which has not extended to involve the muscle layers or lymph nodes (pT1aN0)
• Planned post-operative radiation therapy
• Prior treatment with any of the MTT under investigation in the trial
• Other invasive malignancies, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, have no evidence of that disease for 3 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
• Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol
• Women who are pregnant or breast-feeding
• Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons
• Individuals deprived of liberty or placed under protective custody or guardianship
• Signed a written informed consent form prior to any trial specific procedures (Consent #2)
• Molecular profile showing the tumour harbours at least one targetable molecular alteration with a MTT in the study portfolio (as determined by the trial MTB)
• Surgery performed at least four weeks prior to randomisation with adequate wound healing (in the Investigator's opinion) to allow adjuvant therapy to be initiated
• No measurable disease, as assessed by the investigator: normal post-operative thoracic, abdominal and pelvic CT scan or normal MRI of abdomen and pelvis + normal chest CT performed within 4 weeks prior to randomisation
• ECOG performance status of 0 or 1

Sponsors & Collaborators

• UNICANCER: lead

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma

Interventions

futibatinib; ivosidenib; Capecitabine; zanidatamab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Julien Edeline, MD

  Centre Eugène Marquis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marta Jimenez

CONTACT

+33 (0) 1 44 23 55 58; m-jimenez@unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2026
• First Posted: August 4, 2026
• Study Start (Estimated): January 2, 2027
• Primary Completion (Estimated): July 2, 2033
• Study Completion (Estimated): July 2, 2033
• Last Updated: August 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
• Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.