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

NCT ID: NCT05392608

Last Updated: 2025-09-17

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 130 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-06-02
• Study Completion Date: 2028-03-31

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.

Conditions

Neoplasm, Breast; Congenital, Familial and Genetic Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (one-arm study)

Alpelisib plus fulvestrant beyond progression

Group Type: EXPERIMENTAL

Alpelisib 150 MG Oral Tablet [Piqray]

Intervention Type: DRUG

Alpelisib 300mg once daily (may be reduced to 1dd250 or 1dd200mg in case of toxicity)

Fulvestrant

Intervention Type: DRUG

Fulvestrant 300mg 1x/four weeks

Interventions

Alpelisib 150 MG Oral Tablet [Piqray]

Alpelisib 300mg once daily (may be reduced to 1dd250 or 1dd200mg in case of toxicity)

Intervention Type: DRUG

Fulvestrant

Fulvestrant 300mg 1x/four weeks

Intervention Type: DRUG

Other Intervention Names

Piqray; Faslodex

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Novartis Pharma B.V.

UNKNOWN

Sponsor Role: collaborator

BOOG Study Center

OTHER

Sponsor Role: collaborator

Borstkanker Onderzoek Groep

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vincent V.O. Dezentjé, MD PhD

Role: PRINCIPAL_INVESTIGATOR

NKI-AvL

Inge I.R. Konings, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Amsterdam UMC

Monique M.E.M.M. Bos, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmuc MC

Locations

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

Reinier de Graaf Gasthuis

Delft, , Netherlands

Deventer ziekenhuis

Deventer, , Netherlands

Máxima Medisch Centrum

Eindhoven, , Netherlands

Medisch Spectrum Twente

Enschede, , Netherlands

Admiraal de Ruyter Ziekenhuis

Goes, , Netherlands

Martini Ziekenhuis

Groningen, , Netherlands

Spaarne Gasthuis

Hoofddorp, , Netherlands

Medisch Centrum Leeuwarden

Leeuwarden, , Netherlands

St. Antonius Ziekenhuis

Nieuwegein, , Netherlands

Canisius Wilhelmina Ziekenhuis

Nijmegen, , Netherlands

Maasstad Ziekenhuis

Rotterdam, , Netherlands

Franciscus Gasthuis & Vlietland

Schiedam, , Netherlands

HagaZiekenhuis

The Hague, , Netherlands

Elisabeth-TweeSteden Ziekenhuis

Tilburg, , Netherlands

VieCuri Medisch Centrum

Venlo, , Netherlands

Countries

Netherlands

Other Identifiers

BOOG 2021-01 SEQUEL-Breast

Identifier Type: -

Identifier Source: org_study_id