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Biliary Tract Cancer (BTC)Phase 3SAFIR-IMPACTNCT07745296

Investigating Precision Medicine in the Adjuvant Setting in Biliary Tract Cancer

A Phase 3 study testing Futibatinib, Ivosidenib + Capecitabine and Zanidatamab + Capecitabine in people with Biliary Tract Cancer (BTC), run by UNICANCER.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Biliary Tract Cancer (BTC)
What is being tested?
Futibatinib, Ivosidenib + Capecitabine and Zanidatamab + Capecitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
990 participants
Where
No sites listed yet
Study dates
2 Jan 2027to 2 Jul 2033
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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
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  • 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
  • RANDOMISED PHASE Inclusion criteria
  • 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
  • Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count ≥100 × 10⁹/L, and haemoglobin ≥9 g/dL
  • Adequate liver function: total bilirubin level ≤1.5 × the upper limit of normal (ULN) range (total bilirubin ≤3.0 ULN when the patient has documented Gilbert syndrome), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤2.5 × ULN
  • Adequate renal function: estimated creatinine clearance ≥50 mL/min according to the Cockcroft-Gault formula, or estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
  • Men, and women of childbearing potential (WOCBP) must agree to use adequate contraception for the duration of trial participation and as required after completing study treatment. Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.
  • Note: See Section 5.8.5 for a definition of adequate contraception and required duration of contraceptive use following treatment with individual MTTs.
  • Women of childbearing potential must have a negative serum pregnancy test performed within 3 days before the date of randomisation
  • Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, and other study procedures
  • Affiliated to a social security system or in possession of equivalent private health insurance (according to local country health provision arrangements).
  • Disease relapse occurring at any time prior to randomisation
  • Surgery performed more than 16 weeks prior to randomisation
  • Previous adjuvant treatment, including any systemic treatment, or radiotherapy
  • Inability or unwillingness to swallow pills
  • History of malabsorption syndrome or other condition that would interfere with enteral absorption. For example, active intestine inflammation (e.g., Crohn's disease or ulcerative colitis) requiring immunosuppressive therapy
  • Contraindication or known hypersensitivity to capecitabine or fluorouracil or to the MTT for the molecular alteration found in the patient, or any component in their formulation Note: For patients with multiple target alterations, contraindication to one MTT will not warrant exclusion if MTT to an alternative target is feasible.
  • Radiotherapy within 7 days of randomisation
  • History of severe and unexpected reactions to fluoropyrimidine therapy
  • Known complete dihydropyrimidine dehydrogenase (DPD) deficiency
  • Recent or concomitant treatment with brivudine
  • History of myocardial infarction or unstable angina within 6 months prior to enrolment, troponin levels consistent with myocardial infarction, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, or any history of symptomatic congestive heart failure.
  • Patients with a heart-rate corrected QT interval (using Fridericia's formula) (QTcF) ≥ 450 msec or other factors that increased the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalaemia, family history of long QT interval syndrome).
  • Patients with HBV with HBV-DNA higher than 500IU/mL, active untreated HCV infection, or HIV infection with CD4 below 200. Patients with controlled HBV, HCV and HIV infections are allowed.
  • 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
  • Participation in another therapeutic trial within the 30 days prior to entering the study (participation in an observational trial would be acceptable)
  • 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
  • ADDITIONAL EXCLUSION CRITERIA FOR SPECIFIC MTTs:
  • Futibatinib cohort
  • History and/or current evidence of any of the following disorders:
  • Non-tumour related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator. Blood phosphate concentration should be ≤ ULN at baseline examination.
  • Ectopic mineralization/calcification, including but not limited to soft tissue, kidneys, intestine, or myocardia and lung, considered clinically significant in the opinion of the Investigator
  • Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator
  • Concomitant treatment with strong CYP3A/P-gp inhibitors or strong or moderate CYP3A/P gp inducers where these cannot be substituted for another therapy.
  • Ivosidenib cohort
  • Patients with history of torsade de pointes
  • Concomitant treatment with digoxin where this cannot be substituted for another therapy
  • Concomitant treatment with strong CYP3A4 inducers or dabigatran where these cannot be substituted for another therapy
  • Concomitant treatment with medicinal products known to prolong the QTc interval, or moderate or strong CYP3A4 inhibitors where these cannot be substituted for another therapy
  • Familial history of sudden death or polymorphic ventricular arrhythmia
  • Hypokalaemia, hypomagnesemia or hypocalcaemia where this cannot be corrected by supplementation
  • Zanidatamab cohort
  • Total lifetime anthracycline load exceeding 360 mg/m2 Adriamycin® or equivalent.
  • Use of corticosteroids administered at doses equivalent to >15 mg per day of prednisone within 2 weeks of first zanidatamab dosing unless otherwise approved by the coordinating investigator. Topical, ocular, intra-articular, intranasal, and/or inhalational corticosteroids are permitted.
  • Acute or chronic uncontrolled pancreatitis or Child-Pugh Class B or C liver disease.
  • A history of life-threatening hypersensitivity to monoclonal antibodies or recombinant proteins

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Marta Jimenez contact

+33 (0) 1 44 23 55 58

m-jimenez@unicancer.fr

About this study

Official title: Investigating Precision Medicine in the Adjuvant Setting: a Phase 3 Clinical Trial in Biliary Tract Cancer

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:

Read more
  • 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.
Read the detailed description

This is a multicentre, randomised phase 3, open-label trial to evaluate whether a precision oncology strategy of adjuvant molecular targeted therapy (MTT) can decrease the risk of relapse in the treatment of patients with resected biliary tract cancer (BTC) whose tumour harbours target (ESCAT I) alterations. 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 tumour samples for further translational research. A genetic profile will be obtained from tumour-derived DNA and RNA samples by next-generation sequencing. The trial Molecular Tumour Board will determine whether each patient harbours a targetable molecular alteration for one or more of the trial MTTs. Patients who have sufficiently recovered from surgery, with no measurable disease on post-operative imaging (in the opinion of the investigator), and whose tumour harbours at least one targetable molecular alteration, will be invited to participate in the randomised phase of the trial in which 280 eligible patients will be randomised (2:1) to receive adjuvant therapy with either a matched MTT (combined with SoC or alone depending on the alteration) or to continue 1L-SoC treatment.

Being tested
Futibatinib, Ivosidenib + Capecitabine, Zanidatamab + Capecitabine, Capecitabine (Xeloda)
Keywords
Adjuvant, Targeted therapy, ESCAT, Personalised medicine, Cholangiocarcinoma
Medical subject headings
Biliary Tract Neoplasms, Cholangiocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FutibatinibDrug

    Dose 20 mg once a day (QD)

  • Ivosidenib + CapecitabineDrug

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

  • Zanidatamab + CapecitabineDrug

    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

  • Capecitabine (Xeloda)Drug

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

Study groups in NCT07745296
Study groupRoleWhat they receive
ExperimentalExperimentalMolecular targeted therapy matched to genetic alteration carried by the tumour
Receives: Drug: Futibatinib; Drug: Ivosidenib + Capecitabine; Drug: Zanidatamab + Capecitabine
ControlActive comparatorStandard of care treatment for adjuvant biliary tract cancer
Receives: Drug: Capecitabine (Xeloda)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: From randomisation to disease or death, up to 5 years

Secondary outcomes (8)

  1. Overall Survival

    Time from randomisation to death due to any cause

    Measured: From randomisation to death, up to 5 years

  2. Post-relapse survival

    Time from documented relapse to death due to any cause

    Measured: From randomisation to death, up to 5 years

  3. ctDNA-clearance

    The proportion of patients achieving the transition from ctDNA positivity at inclusion to ctDNA negativity at 24 weeks

    Measured: From randomisation to 24 weeks

  4. Time-to-ctDNA recurrence

    Time from randomisation to the time of ctDNA positivation

    Measured: From randomisation, up to 5 years

  5. Incidence of Adverse Events

    Toxicity will be evaluated according to version 6.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v6.0). NCI-CTCAE is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.

    Measured: From randomisation, up to 5 years

  6. Quality of life questionnaire - Core 30 (QLQ-C30)

    Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.

    Measured: At Baseline, after 42 days (at Cycle 3), after 105 days (at Cycle 6) and after 168 days (end of treatment)

  7. Quality of life Questionnaire - Biliary tract cancer module (QLQ-BIL21)

    This EORTC cholangiocarcinoma and gallbladder cancer specific questionnaire is intended to supplement the QLQ-C30. The QLQ-BIL21 contains 21 items to assess symptoms. All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale.

    Measured: At Baseline, after 42 days (at Cycle 3), after 105 days (at Cycle 6) and after 168 days (end of treatment)

  8. EuroQOL EQ-5D-5L questionnaire

    Developed by the EuroQol group, the self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials consists of a descriptive system and a visual analogue scale (VAS). The EQ-5D-5L descriptive system comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each dimension has 5 levels (1 = "no problems", 2 = "slight problems", 3 = "moderate problems", 4 = "severe problems", and 5 = "extreme problems"). This questionnaire provide a 5-digit score which generate a health state profile. The VAS records the patient's self-rated health on a vertical visual analogue scale where the score range from 0 (The best health you can imagine) to 100 (The worst health you can imagine). The VAS is used as a quantitative measure of health outcome that reflects the patient's own judgement.

    Measured: At Baseline, after 42 days (at Cycle 3), after 105 days (at Cycle 6) and after 168 days (end of treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Aug 2026
  2. Study start2 Jan 2027 (estimated)
  3. Primary completion2 Jul 2033 (estimated)
  4. Study completion2 Jul 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
990 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07745296
Sponsor's protocol ID
UC-GMP-2601 - PRODIGE 122
Other IDs
2025-524960-38-00, 2025
Acronym
SAFIR-IMPACT
Status last verified
Feb 2026
First submitted
8 Jul 2026
Last updated
4 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Futibatinib, Ivosidenib + Capecitabine and Zanidatamab + Capecitabine in people with Biliary Tract Cancer (BTC), run by UNICANCER.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 61 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Marta Jimenez (+33 (0) 1 44 23 55 58, m-jimenez@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Relapse-free survival (time frame: From randomisation to disease or death, up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07745296.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.

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