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

NCT05392608 | Active Not Recruiting Phase 2

• 1 other identifier: BOOG 2021-01 SEQUEL-Breast
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 25

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

Keywords

Hormone receptor positive HER2 negative breast cancer; PIK3CA-activated mutation

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  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.

  From registration to progression, assessed up to 36 months

Secondary Outcomes (4)

• 'On treatment' Progression-free survival (PFS)

  From registration to progression, assessed up to 36 months

• Objective Response Rate

  From registration to progression, assessed up to 36 months

• Clinical Benefit Rate

  From registration to progression, assessed up to 36 months

• Duration of Response (DoR)

  From registration to progression, assessed up to 36 months

Other Outcomes (1)

• Determine circulating tumor DNA (ctDNA) in plasma before and during treatment

  At baseline, 2 weeks of treatment, 8 weeks of treatment and every 8 weeks until disease progression. Assessed up to 36 months

Study Arms (1)

Arm A (one-arm study)

EXPERIMENTAL

Alpelisib plus fulvestrant beyond progression

Drug: Alpelisib 150 MG Oral Tablet [Piqray]; Drug: Fulvestrant

Interventions

Alpelisib 150 MG Oral Tablet [Piqray] DRUG

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

Also known as: Piqray

Arm A (one-arm study)

Fulvestrant DRUG

Fulvestrant 300mg 1x/four weeks

Also known as: Faslodex

Arm A (one-arm study)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Borstkanker Onderzoek Groep: lead
• Novartis Pharma B.V.: collaborator
• BOOG Study Center: collaborator

Study Sites (25)

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, Netherlands

Location

Noordwest Ziekenhuisgroep

Alkmaar, Netherlands

Location

Ziekenhuisgroep Twente

Almelo, Netherlands

Location

Meander Medisch Centrum

Amersfoort, Netherlands

Location

Ziekenhuis Amstelland

Amstelveen, Netherlands

Location

Amsterdam UMC

Amsterdam, Netherlands

Location

Antoni van Leeuwenhoek

Amsterdam, Netherlands

Location

Gelre Ziekenhuizen

Apeldoorn, Netherlands

Location

Rijnstate

Arnhem, Netherlands

Location

Amphia

Breda, Netherlands

Location

Reinier de Graaf Gasthuis

Delft, Netherlands

Location

Deventer ziekenhuis

Deventer, Netherlands

Location

Máxima Medisch Centrum

Eindhoven, Netherlands

Location

Medisch Spectrum Twente

Enschede, Netherlands

Location

Admiraal de Ruyter Ziekenhuis

Goes, Netherlands

Location

Martini Ziekenhuis

Groningen, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, Netherlands

Location

Medisch Centrum Leeuwarden

Leeuwarden, Netherlands

Location

St. Antonius Ziekenhuis

Nieuwegein, Netherlands

Location

Canisius Wilhelmina Ziekenhuis

Nijmegen, Netherlands

Location

Maasstad Ziekenhuis

Rotterdam, Netherlands

Location

Franciscus Gasthuis & Vlietland

Schiedam, Netherlands

Location

HagaZiekenhuis

The Hague, Netherlands

Location

Elisabeth-TweeSteden Ziekenhuis

Tilburg, Netherlands

Location

VieCuri Medisch Centrum

Venlo, Netherlands

Location

MeSH Terms

Conditions

Breast Neoplasms; Genetic Diseases, Inborn

Interventions

Alpelisib; Tablets; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations; 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

• Vincent V.O. Dezentjé, MD PhD

  NKI-AvL

  PRINCIPAL INVESTIGATOR

• Inge I.R. Konings, MD PhD

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

• Monique M.E.M.M. Bos, MD PhD

  Erasmuc MC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2022
• First Posted: May 26, 2022
• Study Start: June 2, 2022
• Primary Completion: January 1, 2026
• Study Completion (Estimated): March 1, 2028
• Last Updated: September 17, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (25)