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Combination of fulvestrant and alpelisib for advanced breast cancer after progression on fulvestrant

SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast): A Phase 2 Study on Fulvestrant Beyond Progression in Combination With Alpelisib for PIK3CA-mutated, Hormone-receptor Positive HER2 Negative Advanced Breast Cancer

Phase 2 Interventional Borstkanker Onderzoek Groep · NCT05392608

This study is testing if combining fulvestrant with alpelisib can help people with advanced breast cancer that has worsened after using fulvestrant, especially those with specific genetic changes.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment130 (estimated)
Ages18 Years and up
SexAll
SponsorBorstkanker Onderzoek Groep Research network
Drugs / interventionschemotherapy, radiation
Locations25 sites (Alkmaar and 24 other locations)
Trial IDNCT05392608 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the effectiveness of combining fulvestrant and alpelisib in patients with hormone receptor-positive, HER2-negative advanced breast cancer who have experienced disease progression on fulvestrant. The study focuses on individuals with PIK3CA mutations and requires prior treatment with a CDK4/6 inhibitor. Participants will continue fulvestrant during the screening period and receive the combination treatment beyond progression after enrollment. The trial aims to evaluate the efficacy of this treatment approach in a multicenter setting.

Who should consider this trial

Good fit: Ideal candidates are adults with HR+ HER2- advanced breast cancer who have progressed on fulvestrant and have a PIK3CA mutation.

Not a fit: Patients with symptomatic visceral spread or those at risk of life-threatening complications may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced breast cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promise with similar combinations in treating advanced breast cancer, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Adult women and men (≥ 18 years of age) with proven diagnosis of adenocarcino-ma of the breast withlocoregional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent andfor whom chemotherapy is not clinically indicated
* Estrogen receptor (ER) expression \>10% and/or progesterone receptor (PR) expression \>10% breast cancerbased on local la-boratory results. Tumor must be HER2- as defined by ASCO-CAP guidelines
* Patients must have progressed on fulvestrant as a preceding treatment line (as first or second line therapy)
* Previous treatment with a CDK4/6 inhibitor in the advanced setting
* The presence of an activating PIK3CA mutation
* Evaluable disease\* as defined per RECIST v.1.1
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2

Exclusion Criteria:

* Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in theshort term
* Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningealdisease as indicated by clinical symptoms, cerebral edema, and/or progressive growth
* Prior treatment with a PI3K /AKT/mTOR inhibitor
* Type 1 diabetes or uncontrolled type 2 diabetes (Hba1C \> 68 mmol/mol)
* Clinically significant, uncontrolled heart disease and/or recent cardiac events

Where this trial is running

Alkmaar and 24 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Neoplasm, BreastCongenital, Familial and Genetic DisordersHormone receptor positive HER2 negative breast cancerPIK3CA-activated mutation
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.