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Active, Not Recruiting

NCT Number: NCT05392608

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Neoplasm, Breast Breast Diseases Breast Neoplasms Congenital, Familial and Genetic Disorders Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Neoplasms Neoplasms by Site Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Jeroen Bosch Ziekenhuis, 's-Hertogenbosch, Netherlands

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Alpelisib 150 MG Oral Tablet [Piqray]

Drug

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

Other names: Piqray

Fulvestrant

Drug

Fulvestrant 300mg 1x/four weeks

Other names: Faslodex

Primary outcomes

  1. Progression-free survival (PFS)

    Time frame: 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 outcomes

  1. 'On treatment' Progression-free survival (PFS)

    Time frame: 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

  2. Objective Response Rate

    Time frame: From registration to progression, assessed up to 36 months

    Described as complete response (CR) or partial response (PR)

  3. Clinical Benefit Rate

    Time frame: From registration to progression, assessed up to 36 months

    Described as stable disease (SD), PR, or CR

  4. Duration of Response (DoR)

    Time frame: From registration to progression, assessed up to 36 months

    Duration of Response

Other outcomes

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

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

    Exploratory endpoint; determine circulating tumor DNA (ctDNA) in plasma before and during treatment, to investigate the prognostic and possibly predictive values of these measures

Sponsors and collaborators

Lead sponsor

Borstkanker Onderzoek Groep

Network

Collaborators

  • BOOG Study Center
  • Novartis Pharma B.V.

Registry information

Official study title

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

Acronym: SEQUEL-Breast

Important dates

Study start
2022
Primary completion
2026
Study completion
2028
First posted
May 26, 2022
Registry last updated
May 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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