Trial Details
Trial status:
In set-up (funded)
Recruitment start date:
Cancer Research UK
Chief Investigator:
Professor John Bridgewater
Recruitment target:
400 (screening phase), 78 (randomised phase)
EudraCT number:
Contact details:
Lay summary:
ABC-10 (SAFIR ABC-10 Precision Medicine)
SAFIR ABC-10 Precision Medicine - Molecular targeted maintenance therapy versus standard of care in advanced biliary cancer: an international, randomised, controlled, open- label, platform phase 3 trial

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.

During the screening phase, patients will receive 4 cycles of standard treatment consisting of cisplatin + gemcitabine:

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)

For those that proceed on to the randomised phase of the trial, and are randomised to receive a molecular targeted therapy, they will receive one of the following drugs that corresponds to their particular targetable molecular alteration: 

Drug: Futibatinib
Dose 20 mg once a day (QD)

Drug: Ivosidenib
Dose 500 mg QD
Other Name: Tibsovo

Drug: Zanidatamab
Dose: Patients

Drug: Trastuzumab
Loading dose 8 mg/kg, then 6 mg/kg Q3W (Combination with neratinib)
Other Name: Zercepac

Drug: Neratinib
Dose: 240 mg QD (combination with trastuzumab)
Other Name: Nerlynx

Drug: Encorafenib
Dose: 450 mg QD (Combination with binimetinib)
Other Name: Braftovi

Drug: Binimetinib
Dose: 45 mg twice a day (BID) (Combination with encorafenib)
Other Name: Mektovi

Drug: Niraparib
Dose: 200 mg QD or 300 mg QD
Other Name: Zejula
Key inclusion/exclusion criteria: For the screening phase, the key inclusion criteria are:
  • Histologically-proven intrahepatic, perihilar or distal cholangiocarcinoma, or gallbladder carcinoma (ampullary carcinoma excluded)
  • De novo or recurrent, locally advanced (non-resectable) or metastatic disease
  • Availability of a suitable archived sample of primary or metastatic tumour tissue (frozen, or FFPE) or able to undergo a biopsy to obtain a suitable malignant tissue sample
  • Aged ≥18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Estimated life expectancy >3 months
  • Candidate for 1L-SoC therapy, or has initiated first cycle of 1L-SoC therapy
The key exclusion criteria are: 
  • Patients who are candidates for locoregional therapy
  • Prior anticancer therapy in the palliative setting. Adjuvant capecitabine allowed if completed ≥183 days prior to study entry
  • Received more than 1 cycle of treatment with 1L-SoC
  • Prior treatment with any of the MTT under investigation in the SAFIR-ABC10 study
  • Current malignancies (other than ABC), 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 5 years or more and are deemed at negligible risk for recurrence, are eligible for the trial
For the randomised phase, the key inclusion criteria are: 
  • 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)
  • Disease control (stable or responsive) after 4 cycles of 1L-SoC, compared to a pre-treatment disease evaluation, as assessed by the investigator
  • ECOG performance status of 0 or 1
  • Presence of at least one evaluable lesion according to RECIST v1.1, or complete response to 12 weeks 1L-SoC
  • Adequate bone marrow, liver, renal and cardiac function
  • Adequate biliary drainage, with no evidence of ongoing infection
The key exclusion criteria are: 
  • Disease progression occurring at any time prior randomisation, or toxicity that led to the discontinuation of the 1L-SoC before 4 full cycles have been delivered
  • Toxicities from 1L-SoC not resolved to Grade ≤2 (according to version 5.0 the National Cancer Institute - Common terminology criteria for adverse events [NCI-CTCAE v5.0]) before randomisation, with the exception of alopecia
  • Contraindication or known hypersensitivity to the MTT for the molecular alteration found in the patient, or any component in their formulation
  • Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers
  • Major surgery within 4 weeks of randomisation
  • Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks of start of study treatment. Stable, treated brain metastases are allowed (defined as subjects who are off steroids and anticonvulsants and are neurologically stable with no evidence of radiographic progression for at least 4 weeks at the time of screening).
  • Known leptomeningeal disease
  • Concurrent malignancy (other than ABC)
  • Known active hepatitis B virus or hepatitis C virus infection or human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
  • 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
Duration of recruitment: 5 years. 

The aim 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.

Trial protocols
Trial protocols must not be applied to patients treated outside trials. UCL CTC can only ensure that approved trial investigators are provided with amendments to protocols.
No protocols have been currently made available for download
Trial documents
No documents have been currently made available for download
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