SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast)

Phase 2

Active, not recruiting

• Conditions: Congenital, Familial and Genetic Disorders; Neoplasm, Breast
• Interventions: Drug: Alpelisib 150 MG Oral Tablet [Piqray]; Drug: Fulvestrant

• Registration Number: NCT05392608
• Lead Sponsor: Borstkanker Onderzoek Groep

Brief Summary

The study is a nationwide, multicenter single-arm phase 2 study. The current phase 2 study investigates the efficacy of the combination of fulvestrant and alpelisib directly after progression on fulvestrant (either in first or second line, with or without previous use of CDK4/6-inhibitor) in patients with HR+ HER2- advanced breast cancer with PIK3CA mutated tumors.

All eligible patients must have progressive disease on fulvestrant as latest treatment line.

Previous treatment with a CDK4/6 inhibitor in first or second line is obligatory. After progressive disease is confirmed, it is important to continue fulvestrant (without CDK4/6 inhibition) during the screening period awaiting study enrollment.

After study enrollment all participants will be treated with alpelisib and fulvestrant beyond progression. Follow-up time will be until progression or death or until a different oncolytic treatment has started (in case no progressive disease during previous fulvestrant and alpelisib treatment has been documented).

Should participants discontinue due to reasons other than progression or death (e.g. toxicity), then they should still be evaluated for disease progression every 8 weeks as per protocol until progression, unless they do not wish to proceed with these screenings, or receive a different oncolytic treatment.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-16
• Study First Submitted QC: 2022-05-23
• Study First Posted: 2022-05-26
• Study Start: 2022-06-02
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-11
• Last Update Posted: 2025-09-17
• Primary Completion: 2026-01
• Study Completion: 2028-03-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 130

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm A (one-arm study)	Alpelisib 150 MG Oral Tablet [Piqray]	Alpelisib plus fulvestrant beyond progression
Arm A (one-arm study)	Fulvestrant	Alpelisib plus fulvestrant beyond progression

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	From registration to progression, assessed up to 36 months	Defined as time from study enrollment to disease progression or death from any cause, with censoring when fulvestrant and alpelisib are stopped and another treatment is initiated without confirmed disease progression.

Secondary Outcome Measures

Name	Time	Method
Clinical Benefit Rate	From registration to progression, assessed up to 36 months	Described as stable disease (SD), PR, or CR
'On treatment' Progression-free survival (PFS)	From registration to progression, assessed up to 36 months	Defined as time from study enrollment to disease progression or death from any cause, with censoring when fulvestrant and alpelisib are stopped earlier than disease progression
Duration of Response (DoR)	From registration to progression, assessed up to 36 months	Duration of Response
Objective Response Rate	From registration to progression, assessed up to 36 months	Described as complete response (CR) or partial response (PR)

Trial Locations

Locations (25)

Jeroen Bosch Ziekenhuis; 🇳🇱 's-Hertogenbosch, Netherlands

Noordwest Ziekenhuisgroep; 🇳🇱 Alkmaar, Netherlands

Ziekenhuisgroep Twente; 🇳🇱 Almelo, Netherlands

Meander Medisch Centrum; 🇳🇱 Amersfoort, Netherlands

Ziekenhuis Amstelland; 🇳🇱 Amstelveen, Netherlands

Amsterdam UMC; 🇳🇱 Amsterdam, Netherlands

Antoni van Leeuwenhoek; 🇳🇱 Amsterdam, Netherlands

Gelre Ziekenhuizen; 🇳🇱 Apeldoorn, Netherlands

Rijnstate; 🇳🇱 Arnhem, Netherlands

Amphia; 🇳🇱 Breda, Netherlands

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