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

NCT05625087 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UC-GMP-2206EU CT
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 44

Brief 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 to ribociclib in combination with fulvestrant (as the continuation of the CDK4/6 inhibitor-fulvestrant strategy) in terms of progression-free survival (PFS).

Conditions

Breast Cancer Stage IV

Keywords

metastatic Breast Cancer; HER2-; RH+; PIK3CA mutated

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (9)

• Overall Survival in the study groups

  From randomization to death, up to 5 years

• Objective response Rate (ORR) in the study groups

  5 years

• Duration of response in the study groups

  5 years

• Clinical Benefit Rate in the study groups

  5 years

• Time to Response in the study groups

  From randomization to death, up to 5 years

Study Arms (2)

ALPELISIB ARM

EXPERIMENTAL

Oral 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

Drug: Alpelisib

RIBOCICLIB ARM

ACTIVE COMPARATOR

Oral 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.

Drug: Ribociclib

Interventions

Alpelisib DRUG

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

Also known as: Fulvestrant

ALPELISIB ARM

Ribociclib DRUG

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

Also known as: Fulvestrant

RIBOCICLIB ARM

Eligibility Criteria

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

You may qualify if:

• 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.
• 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).

You may not qualify if:

• 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.
• 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 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.

Sponsors & Collaborators

• UNICANCER: lead
• Novartis: collaborator
• Breast Cancer Research Foundation: collaborator

Study Sites (44)

CHU Amiens Picardie

Amiens, 80054, France

Location

Clinique de l'Europe Amiens - CTHE

Amiens, 80090, France

Location

Centre Hospitalier d'Auxerre

Auxerre, 89000, France

Location

Sainte Catherine Institut du Cancer Avignon Provence

Avignon, 84918, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64100, France

Location

Centre Hospitalier de Beauvais

Beauvais, 60021, France

Location

Hôpital Simone Veil de Blois

Blois, 41000, France

Location

Institut Bergonié

Bordeaux, 33000, France

Location

Centre Hospitalier de Boulogne-sur-Mer

Boulogne-sur-Mer, 62321, France

Location

CHRU Morvan

Brest, 29200, France

Location

Clinique Pasteur Lanroze - CFRO - Groupe Vivalto Santé

Brest, 29200, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Hôpital NOVO

Cergy-Pontoise, 95303, France

Location

Centre Hospitalier William Morey

Chalon-sur-Saône, 71100, France

Location

Centre Hospitalier de Cholet

Cholet, 49300, France

Location

Pôle Santé République (ELSAN)

Clermont-Ferrand, 63000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Centre Hospitalier Alpes Léman

Contamine-sur-Arve, 74130, France

Location

Clinique de Flandre

Coudekerque-Branche, 59210, France

Location

CHI Fréjus-Saint-Raphaël

Fréjus, 83608, France

Location

Groupe Hospitalier Mutualiste de Grenoble (GHMG)

Grenoble, 38028, France

Location

CHD Vendée

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier de Versailles - Hôpital André Mignot

Le Chesnay, 78150, France

Location

Polyclinique de Limoges - Site François Chénieux

Limoges, 87000, France

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital privé Jean Mermoz

Lyon, 69008, France

Location

Clinique de la Sauvegarde

Lyon, 69009, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

ICM Val d'Aurelle

Montpellier, 34298, France

Location

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

Nancy, 54100, France

Location

Clinique Hartmann

Neuilly-sur-Seine, 92200, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Hôpital Saint-Louis

Paris, 75010, France

Location

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, 75020, France

Location

Centre Hospitalier de Pau

Pau, 64046, France

Location

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

Plérin, 22190, France

Location

Institut Godinot

Reims, 51100, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

CHP Saint-Grégoire - Groupe Vivalto Santé

Saint-Grégoire, 35760, France

Location

Clinique Sainte-Anne - GH Saint-Vincent

Strasbourg, 67000, France

Location

Hôpitaux du Léman

Thonon-les-Bains, 74200, France

Location

Institut Claudius Regaud - IUCT-O

Toulouse, 31059, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54519, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Alpelisib; Fulvestrant; ribociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Fabrice ANDRE

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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)

Study Record Dates

• First Submitted: November 14, 2022
• First Posted: November 22, 2022
• Study Start: October 19, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: August 20, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (44)