Informations générales (source: ClinicalTrials.gov)
Molecular Targeted Maintenance Therapy Versus Standard of Care in Advanced Biliary Cancer: an International, Randomised, Controlled, Open-label, Platform Phase 3 Trial (SAFIR-ABC10)
Interventional
Phase 3
UNICANCER (Voir sur ClinicalTrials)
juillet 2024
juin 2028
24 avril 2025
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Antoine HOLLEBECQUE | 01/07/2024 09:44:44 | Contacter | ||
| HOPITAL FOCH | Jaafar BENNOUNA | 05/05/2025 07:12:13 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Beaujon | Mohamed BOUATTOUR, MD | Contact (sur clinicalTrials) | |||
| AP-HP - Hôpital Saint Antoine | Helene BOUSSION DESLOGES, MD | Contact (sur clinicalTrials) | |||
| GRPE HOSP DIACONESSES-CROIX ST-SIMON | Olivier DUBREUIL, MD | Contact (sur clinicalTrials) | |||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| APHM - CHU La Timone - Marseille - France | Laétitia DAHAN, MD | Contact (sur clinicalTrials) | |||
| APHP - Hopital Henri Mondor - Créteil - France | Christophe TOURNIGAND, MD | Contact (sur clinicalTrials) | |||
| Centre Antoine Lacassagne - Nice - France | Ludovic EVESQUE, MD | Contact (sur clinicalTrials) | |||
| Centre Eugène Marquis - Rennes - France | Julien Edeline | Contact (sur clinicalTrials) | |||
| Centre François Baclesse - Caen - France | Stéphane CORBINAIS | Contact (sur clinicalTrials) | |||
| Centre Jean Perrin - Clermont-Ferrand - France | Florence OSAER-POLYCARPE | Contact (sur clinicalTrials) | |||
| Centre Leon Bérard - Lyon - France | Philippe CASSIER, MD | Contact (sur clinicalTrials) | |||
| Centre Oscar Lambret - Lille - France | Aurélien CARNOT, MD | Contact (sur clinicalTrials) | |||
| CH Cornouaille - Quimper - France | Christophe AGNELLO, MD | Contact (sur clinicalTrials) | |||
| CH de Pau - Pau - France | Juliette THAURY, MD | Contact (sur clinicalTrials) | |||
| CH Valence - Valence - France | Hélène FOISY, MD | Contact (sur clinicalTrials) | |||
| CHRU de Nancy - Vandœuvre-lès-Nancy - France | Marie MULLER, MD | Contact (sur clinicalTrials) | |||
| CHU Amiens Picardie - Amiens - France | Vincent HAUTEFEUILE, MD | Contact (sur clinicalTrials) | |||
| CHU Charles Nicolle - Rouen - France | Frederic DI FIORE, MD | Contact (sur clinicalTrials) | |||
| CHU d'Angers - Angers - France | Carole Vitellius | Contact (sur clinicalTrials) | |||
| CHU de Besançon - Besançon - France | Christophe BORG | Contact (sur clinicalTrials) | |||
| CHU de Bordeaux - Hôpital Haut-Leveque - Bordeaux - France | Jean-Frédéric BLANC | Contact (sur clinicalTrials) | |||
| CHU de Dijon - Dijon - France | Sylvain MANFREDI | Contact (sur clinicalTrials) | |||
| CHU de Reims - Reims - France | Elia GIGANTE, MD | Contact (sur clinicalTrials) | |||
| CHU Dupuytren - Limoges - France | Frédéric THUILLIER, MD | Contact (sur clinicalTrials) | |||
| CHU Estaing de Clermont Ferrand - Clermont-Ferrand - France | Marine JARY, MD | Contact (sur clinicalTrials) | |||
| CHU Grenoble Alpes - Grenoble - France | Gael ROTH, MD | Contact (sur clinicalTrials) | |||
| CHU Lille - Lille - France | Anthony TURPIN, MD | Contact (sur clinicalTrials) | |||
| CHU Nantes - Hôtel Dieu - Nantes - France | Yann TOUCHEFEU, MD | Contact (sur clinicalTrials) | |||
| CHU Poitiers - Poitiers - France | David TOUGERON, MD | Contact (sur clinicalTrials) | |||
| CHU Toulouse - Toulouse - France | Nadim FARES, MD | Contact (sur clinicalTrials) | |||
| Clinique Privée Jean Mermoz - Lyon - France | Lea CLAVEL, MD | Contact (sur clinicalTrials) | |||
| Groupe hospitalier mutaliste de Grenoble - Institut Daniel Hollard - Grenoble - France | Camille HERVE, MD | Contact (sur clinicalTrials) | |||
| Gustave Roussy - Villejuif - France | Antoine Hollebecque | Contact (sur clinicalTrials) | |||
| Hôpital Européen - Marseille - France | Nicolas BARRIERE, MD | Contact (sur clinicalTrials) | |||
| Hôpital Foch - Suresnes - France | Jaafar BENNOUNA, MD | Contact (sur clinicalTrials) | |||
| Hospices Civils de Lyon - Croix Rousse - Lyon - France | Marielle GUILLET, MD | Contact (sur clinicalTrials) | |||
| Institut Curie - Saint Cloud - Saint Cloud - France | Cindy NEUZILLET, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancer de Montpellier - Montpellier - France | Fabienne PORTALES, MD | Contact (sur clinicalTrials) | |||
| Institut de cancerologie de l'Ouest - Angers - Angers - France | Victor SIMMET, MD | Contact (sur clinicalTrials) | |||
| Institut de Cancerologie de l'Ouest - Saint-Herblain - France | Amélie MALLET, MD | Contact (sur clinicalTrials) | |||
| Institut du Cancer Avignon Provence - Avignon - France | Clémence TOULLEC | Contact (sur clinicalTrials) | |||
| Institut Jean Godinot - Reims - France | Damien BOTSEN, MD | Contact (sur clinicalTrials) | |||
| Institut Paoli Calmettes - Marseille - France | Simon LAUNAY, MD | Contact (sur clinicalTrials) | |||
| Institute Mutualiste Montsouris - Paris - France | David MALKA, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
1. Signed a written informed consent form prior to any trial specific procedures
(Consent #1)
2. Histologically-proven intrahepatic, perihilar or distal cholangiocarcinoma, or
gallbladder carcinoma (ampullary carcinoma excluded)
3. De novo or recurrent, locally advanced (non-resectable) or metastatic disease
4. 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
5. Aged ≥18 years
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Estimated life expectancy >3 months
8. Candidate for 1L-SoC therapy, or has initiated first cycle of 1L-SoC therapy
9. Affiliated to a social security system or in possession of equivalent private health
insurance (according to local country health provision arrangements).
1. Signed a written informed consent form prior to any trial specific procedures
(Consent #1)
2. Histologically-proven intrahepatic, perihilar or distal cholangiocarcinoma, or
gallbladder carcinoma (ampullary carcinoma excluded)
3. De novo or recurrent, locally advanced (non-resectable) or metastatic disease
4. 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
5. Aged ≥18 years
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Estimated life expectancy >3 months
8. Candidate for 1L-SoC therapy, or has initiated first cycle of 1L-SoC therapy
9. Affiliated to a social security system or in possession of equivalent private health
insurance (according to local country health provision arrangements).
1. Contraindication to 1L-SoC
2. Patients who are candidates for locoregional therapy
3. Contraindication to tumour biopsy in the absence of suitable archived sample of
tumour tissue
4. Prior anticancer therapy in the palliative setting. Adjuvant capecitabine allowed if
completed ≥ 183 days prior to study entry
5. Received more than 1 cycle of treatment with 1L-SoC
6. Prior treatment with any of the MTT under investigation in the SAFIR-ABC10 study
7. 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
8. 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
9. Women who are pregnant or breast-feeding
10. Patients unwilling or unable to comply with the medical follow-up required by the
trial because of geographic, familial, social, or psychological reasons
11. Individuals deprived of liberty or placed under protective custody or guardianship
RANDOMISED TRIAL
Inclusion Criteria:
1. Signed a written informed consent form prior to any trial specific procedures
(Consent #2)
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)
3. Disease control (stable or responsive) after 4 cycles of 1L-SoC, compared to a
pre-treatment disease evaluation, as assessed by the investigator
4. ECOG performance status of 0 or 1
5. Presence of at least one evaluable lesion according to RECIST v1.1, or complete
response to 12 weeks 1L-SoC
6. Adequate bone marrow function: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L,
platelet count ≥100 × 10⁹/L, and haemoglobin ≥9 g/dL
7. 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 (AST and ALT ≤5 ULN when documented tumour liver involvement)
8. Adequate renal function: estimated creatinine clearance ≥ 60 mL/min according to the
Cockcroft-Gault formula
9. Adequate cardiac function: left ventricular ejection fraction ≥50% at baseline as
determined by either echocardiogram or multigated acquisition scan (MUGA)
10. Adequate biliary drainage, with no evidence of ongoing infection
11. 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.
12. Women of childbearing potential must have a negative serum pregnancy test performed
within 3 days before the date of randomisation
13. 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
14. Affiliated to a social security system or in possession of equivalent private health
insurance (according to local country health provision arrangements)
Exclusion Criteria:
1. 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
2. Toxicities from 1L-SoC not resolved to Grade ≤ 1 (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
3. Contraindication or known hypersensitivity 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.
4. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers
5. Major surgery within 4 weeks of randomisation
6. Radiotherapy within 7 days of randomisation
7. 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).
8. Clinically significant cardiovascular disease (recent acute myocardial infarction,
treated congestive heart failure [2 or above on the New York Heart Association
functional classification scale], recent thromboembolic or cerebrovascular events
[within 12 weeks, excepted if related to indwelling catheter], known prolonged QT
syndrome).
9. Cardiorespiratory pathologies where hyperhydration is contraindicated.
10. Manifestation of tinnitus and/or hearing loss since initiation of cisplatin therapy.
11. Known leptomeningeal disease. If leptomeningeal disease has been reported
radiographically on baseline magnetic responance imaging (MRI), but is not suspected
clinically by the investigator, the subject must be free of neurological symptoms.
12. Concurrent malignancy (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
13. Concomitant treatment with phenytoin in prophylactic use where this cannot be
substituted for another therapy
14. Known active hepatitis B virus or hepatitis C virus infection or human
immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
15. 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
16. Women who are pregnant or breast-feeding
17. Participation in another therapeutic trial within the 30 days prior to entering the
study. Participation in an observational trial would be acceptable
18. Patients unwilling or unable to comply with the medical follow-up required by the
trial because of geographic, familial, social, or psychological reasons
19. Individuals deprived of liberty or placed under protective custody or guardianship
ADDITIONAL EXCLUSION CRITERIA FOR SPECIFIC MTTs:
Patients assigned to receive oral therapies:
1. Inability or unwillingness to swallow pills
2. 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
Futibatinib:
1. History and/or current evidence of any of the following disorders:
1. Non-tumour related alteration of the calcium-phosphorus homeostasis that is
considered clinically significant in the opinion of the Investigator
2. 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
3. Retinal or corneal disorder confirmed by retinal/corneal examination and
considered clinically significant in the opinion of the Investigator
2. 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:
1. Patients with history of torsade de pointes
2. Concomitant treatment with digoxin where this cannot be substituted for another
therapy
3. 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, hypokalemia, family history of long QT interval
syndrome)
4. Concomitant treatment with strong CYP3A4 inducers or dabigatran where these cannot
be substituted for another therapy
5. 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
6. Familial history of sudden death or polymorphic ventricular arrhythmia.
7. Hypokalemia, hypomagnesemia or hypocalcemia where this cannot be corrected by
supplementation
Zanidatamab:
1. Treatment with anthracyclines within 90 days before first dose of zanidatamab and/or
total lifetime load exceeding 360 mg/m2 Adriamycin® or equivalent
2. 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
3. QTcF > 470 ms
4. History of myocardial infarction or unstable angina within 6 months prior to
enrollment, 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
5. Acute or chronic uncontrolled pancreatitis or Child-Pugh Class C liver disease
6. Clinically significant infiltrative pulmonary disease not related to lung metastases
7. A history of life-threatening hypersensitivity to monoclonal antibodies or
recombinant proteins
Neratinib & trastuzumab:
1. Patients with severe hepatic impairment (Child-Pugh Class C)
2. Co-administration with the following medical products that are strong inducers of
the CYP3A4/P-gp isoform of cytochrome P450, such as carbamazepine, phenytoin
(antiepileptics), St John's wort (Hypericum perforatum) or rifampicin
(antimycobacterial)
3. Patients who are experiencing dyspnoea at rest due to complications of advanced
malignancy or co-morbidities
4. Hypersensitivity to murine proteins
5. Current active pneumonitis within 90 days of receiving trastuzumab or a known
history of interstitial lung disease
Encorafenib & binimetinib:
1. Patients with a history or current evidence of retinal vein occlusion or risk
factors for retinal vein occlusion (e.g., uncontrolled glaucoma or history of
hyperviscosity or hypercoagulability syndrome)
2. Patients with concurrent neuromuscular disorders associated with elevated creatine
phosphokinase (>ULN)
3. Patients with hypokalemia, hypomagnesemia, or hypocalcemia (i.e. Serum potassium,
magnesium or calcium < lower normal limit)
4. Patients with a QTcF ≥ 450 msec for men, or ≥ 470 msec for women
5. Current or expected use of a strong inhibitor of CYP3A4