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AzTrials

Breast Cancer Stage IVPhase 2SAFIR 03NCT05625087

Detection of Tumor DNA in the Blood of Patients Receiving Standard Therapy for Hormone Receptor-positive (HR+) Non-HER2 Expressing (HER2-) Metastatic Breast Cancer as a Tool to Select Those Who May Benefit From the Next Course of Fulvestrant in Combination With Alpelisib or Ribociclib

A Phase 2 study testing Alpelisib and Ribociclib in people with Breast Cancer Stage IV, run by UNICANCER at 44 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

After an initial screening phase (SAFIR 03 - SCREENING) to identify patients with blood circulating mutated-PIK3CA tumours persistent, patients will be enrolled in the treatment phase of SAFIR 03 (SAFIR 03 - ARRIBA) that was designed as a randomised, open-label, multicentre, phase II study, for comparison of alpelisib… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer Stage IV
What is being tested?
Alpelisib and Ribociclib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
44 sitesFrance
Study dates
19 Oct 2023to 20 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Patient must have signed a written informed consent prior to any study-specific screening procedures (the consent form specifically for the screening phase must be signed).
  • Patient is ≥18 years of age.
  • Patient has an histologically or cytologically confirmed metastatic breast cancer.
  • Patient has a HER2- breast cancer (without HER2 overexpression according to the ASCO-CAP 2018 guidelines).
  • Patient has hormone receptor-positive (HR+) breast cancer, defined as having oestrogen receptor (ER) and/or progesterone receptor (PR) expression in ≥10% of tumour cells.
  • Patient had a metastatic relapse during or within 1 year after termination of the adjuvant endocrine therapy.
Show all 40Show fewer
  • Patient has not yet been treated in the metastatic breast cancer setting.
  • Patient is eligible for a first-line treatment with a marketed CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) in combination with fulvestrant, according to its marketing authorisation.
  • Eastern Cooperative Oncology Group (ECOG) performance status is ≤1.
  • Patient has an adequate bone marrow and organ function.
  • Measurable or evaluable disease according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1).
  • Patients must be 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.
  • Patient must be affiliated to the national social security (or equivalent).
  • Patient must have signed a written informed consent prior to any procedures for the randomised study phase (the consent form specifically for the randomised study phase must be signed).
  • Patient has a circulating PIK3CA level of exon 4, 9 or 20 mutant* of PIK3CA ctDNA determined by circulating tumour DNA (ctDNA) assay after 4 weeks of treatment with any CDK4/6 inhibitor combined with fulvestrant.
  • Patient must have discontinued CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) at least 7 days before randomisation.
  • ECOG performance status is ≤1.
  • Patient's life expectancy is deemed ≥3 months.
  • Patient has an adequate bone marrow and organ function as defined by the following laboratory values:
  • Absolute neutrophil count (ANC) ≥1500/mm³,
  • Platelet count ≥100,000/mm³,
  • Haemoglobin ≥9.0 g/dL,
  • International normalised ratio (INR) ≤1.5 (unless the participant is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to the first dose of study drug),
  • Serum creatinine ≤1.5 × upper limit of normal (ULN) or creatinine clearance ≥50 mL/min,
  • Total bilirubin ≤2× ULN (<3 ULN with documented Gilbert's disease) or direct bilirubin ≤ 1.5 × ULN,
  • aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or <5.0 x ULN if patient has liver metastasis,
  • Fasting Serum amylase ≤ 2 × ULN,
  • Fasting Serum lipase ≤ ULN,
  • Fasting plasma glucose (FPG) ≤140 mg/dL (or ≤7.7 mmol/L) and glycosylated haemoglobin (HbA1c) ≤6.4%.
  • Participant must have the following laboratory values within normal limits or corrected to within normal limits with supplements before randomisation
  • Potassium
  • Magnesium
  • Total Calcium (corrected for serum albumin)
  • Patient with parameters of standard 12-lead ECG (defined as the mean of triplicate ECGs performed) as follows, before randomisation:
  • QTcF interval <450ms (using Fridericia's correction),
  • Resting heart rate between 50-90 bpm.
  • Women of childbearing potential must have a negative serum pregnancy test result within 14 days of enrolment in the randomised trial phase.
  • Men or Women of childbearing potential must agree to the use of effective contraceptive for the study duration and for at least 2 year after the last dose of study treatment for women, and at least 21 days for men.
  • Patients must be 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.
  • Also numbered exon 5, 10 and 21 according to recent classification: Ensembl Transcript ID: ENST00000263967.4, RefSeq: NM_006218.4.

Who cannot join

  • Prior exposure to PIK3CA-AKT or CDK4/6 inhibitors.
  • Patient that has initiated the CDK4/6 inhibitor treatment.
  • Patient with spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for ≥30 days before initiating the study treatment).
  • Participant with an established diagnosis of diabetes mellitus type I or not controlled type II (based on FG and HbA1c).
  • Patient unable to swallow tablets.
  • Patient with known hypersensitivity to any of the study treatment excipients, in particular patients with allergies to soya or peanuts.
Show all 41Show fewer
  • Patients with a history of malabsorption syndrome or other condition that may interfere with enteral absorption: including but not limited to active intestine inflammation (e.g., Crohn's disease or ulcerative colitis) requiring immunosuppressive therapy.
  • Patient with any condition/disease for which the investigator considers that participating in the study is inappropriate or that may jeopardize treatment and protocol compliance.
  • Patient deprived of liberty or under the authority of a tutor.
  • RANDOMISED PHASE ( SAFIR 03 -ARRIBA)
  • Patient is eligible to chemotherapy because of visceral crisis.
  • Pregnant or lactating women.
  • Patient has received more than 2 cycles of the ongoing CDK4/6 inhibitor treatment combined with fulvestrant before randomisation.
  • Patient has interrupted the ongoing CDK4/6 inhibitor treatment for more than 14 days before randomisation.
  • Patient has evidence of clinical or radiological disease progression before randomisation.
  • Patient has unresolved adverse events (grade ≥1), except alopecia and grade ≥2 unresolved adverse events related to fulvestrant or the LH-RH analogue which are acceptable to randomisation.
  • Patient is considered at high medical risk because of severe or uncontrolled systemic disease, including but not limited to diabetes mellitus, clinically significant pulmonary disease, clinically significant neurological disorder, chronic pancreatitis, chronic active hepatitis, active untreated/uncontrolled fungal, bacterial, or viral infections, as well as known active viral infections with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
  • Participant has currently documented pneumonitis/interstitial lung disease (the chest CT scan performed before start of study treatment for the purpose of tumour assessment should be reviewed to confirm that there are no relevant pulmonary complications present).
  • Participant has a history of severe cutaneous reaction, such as Stevens-Johnson Syndrome (SJS), Erythema Multiforme (EM), Toxic Epidermal Necrolysis (TEN), or Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
  • Participant with unresolved osteonecrosis of the jaw.
  • Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities including any of the following:
  • Uncontrolled hypertension,
  • Symptomatic congestive heart failure: New York Heart Association (NYHA) class ≥2,
  • Unstable angina pectoris,
  • Stroke or myocardial infarction within the 6 months before randomisation,
  • Serious cardiac arrhythmia requiring treatment, except treated atrial fibrillation and paroxysmal supraventricular tachycardia, or conduction abnormality for which the patient is no longer at risk of serious arrhythmia (e.g., Patient with Wolff-Parkinson-White syndrome treated with surgical ablation),
  • Left ventricular ejection fraction (LVEF) <50% by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) before randomisation.
  • Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following before randomisation:
  • Presence of risk factors for Torsades de Pointe, including uncorrected hypokalaemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia,
  • Concomitant use of medication(s) known to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to initiating the study treatment) or cannot be replaced by a safe alternative,
  • Unable to determine the QTcF (using Fridericia's correction),
  • Systolic blood pressure (SBP) >160 mmHg or <90 mmHg.
  • Patient who has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug, or who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom ≥ 25% of the bone marrow was irradiated
  • Patient is currently consuming any of the following foods, supplements, herbal preparations or medications that cannot be discontinued within 7 days of initiating the study treatment:
  • Known strong inducers or inhibitors of CYP3A4/5 (including grapefruits),
  • Medications predominantly metabolised through CYP3A4/5, with a narrow therapeutic window,
  • Patient has known hypersensitivity to any of the study treatment excipients, in particular patients with allergies to soya or peanuts.
  • Patient is or plans to participate in another interventional therapeutic clinical trial. Concurrent participation in an observational study is acceptable.
  • Patient has malignancies, other than that under study, except for adequately treated cone-biopsied in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, with no evidence of relapse/recurrence within ≥5 years, and at negligible risk for recurrence are eligible for the study.
  • Patient has any condition/disease, for which the investigator considers that participating in the trial is inappropriate or that may jeopardize treatment and protocol compliance.
  • Patient deprived of liberty or under the authority of a tutor.

Trial locations and contacts

44 sites in 1 country.

44 sites in 1 country

France44 sites

  • CHU Amiens Picardie

    Amiens, 80054

  • Clinique de l'Europe Amiens - CTHE

    Amiens, 80090

  • Centre Hospitalier d'Auxerre

    Auxerre, 89000

  • Sainte Catherine Institut du Cancer Avignon Provence

    Avignon, 84918

  • Centre Hospitalier de la Côte Basque

    Bayonne, 64100

  • Centre Hospitalier de Beauvais

    Beauvais, 60021

  • Hôpital Simone Veil de Blois

    Blois, 41000

  • Institut Bergonié

    Bordeaux, 33000

  • Centre Hospitalier de Boulogne-sur-Mer

    Boulogne-sur-Mer, 62321

  • CHRU Morvan

    Brest, 29200

  • Clinique Pasteur Lanroze - CFRO - Groupe Vivalto Santé

    Brest, 29200

  • Centre François Baclesse

    Caen, 14000

  • Hôpital NOVO

    Cergy-Pontoise, 95303

  • Centre Hospitalier William Morey

    Chalon-sur-Saône, 71100

  • Centre Hospitalier de Cholet

    Cholet, 49300

  • Pôle Santé République (ELSAN)

    Clermont-Ferrand, 63000

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

  • Centre Hospitalier Alpes Léman

    Contamine-sur-Arve, 74130

  • Clinique de Flandre

    Coudekerque-Branche, 59210

  • CHI Fréjus-Saint-Raphaël

    Fréjus, 83608

  • Groupe Hospitalier Mutualiste de Grenoble (GHMG)

    Grenoble, 38028

  • CHD Vendée

    La Roche-sur-Yon, 85925

  • Centre Hospitalier de Versailles - Hôpital André Mignot

    Le Chesnay, 78150

  • Polyclinique de Limoges - Site François Chénieux

    Limoges, 87000

  • Centre Léon Bérard

    Lyon, 69008

  • Hôpital privé Jean Mermoz

    Lyon, 69008

  • Clinique de la Sauvegarde

    Lyon, 69009

  • Institut Paoli Calmettes

    Marseille, 13009

  • ICM Val d'Aurelle

    Montpellier, 34298

  • Medipôle de Nancy - COG-ILC (Polyclinique de Gentilly)

    Nancy, 54100

  • Clinique Hartmann

    Neuilly-sur-Seine, 92200

  • Centre Antoine Lacassagne

    Nice, 06189

  • Hôpital Saint-Louis

    Paris, 75010

  • Groupe Hospitalier Diaconesses Croix Saint-Simon

    Paris, 75020

  • Centre Hospitalier de Pau

    Pau, 64046

  • Hôpital Privé des Côtes-d'Armor (HPCA) - Cario

    Plérin, 22190

  • Institut Godinot

    Reims, 51100

  • Centre Eugène Marquis

    Rennes, 35042

  • CHP Saint-Grégoire - Groupe Vivalto Santé

    Saint-Grégoire, 35760

  • Clinique Sainte-Anne - GH Saint-Vincent

    Strasbourg, 67000

  • Hôpitaux du Léman

    Thonon-les-Bains, 74200

  • Institut Claudius Regaud - IUCT-O

    Toulouse, 31059

  • Institut de Cancérologie de Lorraine

    Vandœuvre-lès-Nancy, 54519

  • Gustave Roussy

    Villejuif, 94805

Other trials in France

About this study

Official title: A ctDNA Screening Program in Patients With HR+, HER2- Metastatic Breast Cancer for Detection of High-risk Relapse Patients on Any CDK4/6 Inhibitor and a Randomised Phase II Study Comparing Alpelisib Combined With Fulvestrant to Ribociclib Combined With Fulvestrant, in Patients With Persistent Targetable PIK3CA Mutations

After an initial screening phase (SAFIR 03 - SCREENING) to identify patients with blood circulating mutated-PIK3CA tumours persistent, patients will be enrolled in the treatment phase of SAFIR 03 (SAFIR 03 - ARRIBA) that was designed as a randomised, open-label, multicentre, phase II study, for comparison of alpelisib to ribociclib in combination with fulvestrant (as the continuation of the CDK4/6 inhibitor-fulvestrant strategy) in terms of progression-free survival (PFS).

Read the detailed description

INDICATION The population eligible to the screening phase is composed of all women or men with HR+, HER2- metastatic breast cancer who are eligible for first-line treatment with a cyclin-dependent kinases (CDK) 4/6 inhibitor combined with fulvestrant (and a luteinizing hormone realeasing hormone (LH-RH) analogue in men and premenopausal women) in the context of the standard healthcare management. The screening will identify patients with high risk of relapse on any CDK4/6 inhibitor thanks to ctDNA kinetic between baseline and 4 weeks of treatment. The purpose is to early adapt the therapeutic intervention for ctDNA no drop patient to prevent from relapse. This study will propose an intervention for PIK3CA mutated patients with alpelisib vs. ribociclib. Other therapeutic approaches might be proposed to patients with wild type PIK3CA through other protocols.

The randomised study phase will include patients with persistent mutations on exons 4, 9 or 20* of PIK3CA ctDNA after 4 weeks of treatment with any CDK4/6 inhibitor-fulvestrant in first-line setting.

Being tested
Alpelisib, Ribociclib
Keywords
metastatic Breast Cancer, HER2-, RH+, PIK3CA mutated
Medical subject headings
Breast Neoplasms

What participants receive

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

  • AlpelisibDrug

    Also called Fulvestrant

    Alpelisib 300 mg once daily + fulvestrant 500 mg every 28 days

  • RibociclibDrug

    Also called Fulvestrant

    Ribocilcib 600 mg once daily 3 weeks on/1 week off + fulvestrant 500 mg every 28 days

Study groups in NCT05625087
Study groupRoleWhat they receive
ALPELISIB ARMExperimentalOral alpelisib (300 mg daily, in 28-day cycle) and fulvestrant as per standard practice. Moreover, men and premenopausal women will receive an LH-RH analogue (goserelin, leuprorelin, or triptorelin) every 28 days ±3 days, as per standard practice
Receives: Drug: Alpelisib
RIBOCICLIB ARMActive comparatorOral ribociclib (600 mg daily, 3 weeks on, then 1 week off treatment in 28-day cycles) and fulvestrant as per standard practice. Moreover, men and premenopausal women will receive an LH-RH analogue (goserelin, leuprorelin, or triptorelin) every 28 days ±3 days, as per standard practice.
Receives: Drug: Ribociclib

What is being measured

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

  1. Progression-Free Survival in the study groups

    The PFS is the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.

    Measured: From randomization to disease progression or death, up to 5 years

Secondary outcomes (9)

  1. Overall Survival in the study groups

    Overall survival (OS) is the length of time from randomization that patients enrolled in the study are still alive.

    Measured: From randomization to death, up to 5 years

  2. Objective response Rate (ORR) in the study groups

    Objective response rate (ORR) is the percentage of patients with a best response during treatment being either complete response (CR) or partial response (PR).

    Measured: 5 years

  3. Duration of response in the study groups

    Duration of response (DoR) is defined as the time interval from the date of first documented CR or PR to the date of first documented disease progression or death, from any cause.

    Measured: 5 years

  4. Clinical Benefit Rate in the study groups

    Clinical benefit rate (CBR) is defined as the proportion of patients with a best overall response of CR, PR, or stable disease during treatment.

    Measured: 5 years

  5. Time to Response in the study groups

    Time to response (TTR) is defined, for subjects with an objective response (OR), as the time from randomisation to the first documentation of OR which is subsequently confirmed.

    Measured: From randomization to death, up to 5 years

  6. To validate that randomised patients with residual PIK3CA on ctDNA present a poor outcome compare to non-randomised patient

    For this outcome, PFS is defined as the time interval between the date of initiation of standard of care to the date of the first documented disease progression or death, whatever the cause.

    Measured: From the date of initiation of standard of care to death, up to 5 years

  7. Safety in each study groups.

    The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) 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: Throughout study completion, up to 5 years

  8. Overall Survival (OS) in non-randomised patients

    For non-randomised patients, OS is the length of time from the date of initiation of standard of care that patients enrolled in the study are still alive.

    Measured: From the date of initiation of standard of care to death of any cause, up to 5 years

  9. Progression Free Survival (PFS) in non-randomised patients

    For non-randomised patients, PFS is the length of time during and after the treatment of a disease with the standard of care that a patient lives with the disease but it does not get worse.

    Measured: From randomization to death, up to 5 years

Timeline

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

  1. First posted22 Nov 2022
  2. Study start19 Oct 2023
  3. Primary completion30 Mar 2025
  4. Study completion20 Jan 2026

Why it stopped: poor accrual

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
After an initial screening phase (SAFIR 03 - SCREENING) to identify patients with blood circulating mutated-PIK3CA tumours persistent, patients will be enrolled in the treatment phase of SAFIR 03 (SAFIR 03 - ARRIBA) that was designed as a randomised, open-label, multicentre, phase II study, for comparison of alpelisib to ribociclib in combination with fulvestrant (as the continuation of the CDK4/6 inhibitor-fulvestrant strategy)
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05625087
Sponsor's protocol ID
UC-GMP-2206
Other IDs
EU CT
Acronym
SAFIR 03
Status last verified
Sep 2026
First submitted
14 Nov 2022
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpelisib and Ribociclib in people with Breast Cancer Stage IV, run by UNICANCER at 44 sites in France.

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 40 inclusion and 41 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: stopped early, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

The study was stopped early (reason given: poor accrual). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival in the study groups (time frame: From randomization to disease progression 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 NCT05625087.

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 14 Oct 2026.

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