Clinical trial NCT05392608: SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast)
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Neoplasm, Breast
Congenital, Familial and Genetic Disorders
Keywords: Hormone receptor positive HER2 negative breast cancer
PIK3CA-activated mutation
Lead sponsor: Borstkanker Onderzoek Groep
Sponsor class: NETWORK
Collaborators: name: Novartis Pharma B.V.
name: BOOG Study Center
First posted: 2022-05-26
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: From registration to progression, assessed up to 36 months
Secondary outcomes:
measure: 'On treatment' Progression-free survival (PFS)
timeFrame: From registration to progression, assessed up to 36 months
measure: Objective Response Rate
timeFrame: From registration to progression, assessed up to 36 months
measure: Clinical Benefit Rate
timeFrame: From registration to progression, assessed up to 36 months
measure: Duration of Response (DoR)
timeFrame: From registration to progression, assessed up to 36 months
Other outcomes:
measure: Determine circulating tumor DNA (ctDNA) in plasma before and during treatment
timeFrame: At baseline, 2 weeks of treatment, 8 weeks of treatment and every 8 weeks until disease progression. Assessed up to 36 months
Locations:
city: Alkmaar
country: Netherlands
facility: Noordwest Ziekenhuisgroep
city: Almelo
country: Netherlands
facility: Ziekenhuisgroep Twente
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amstelveen
country: Netherlands
facility: Ziekenhuis Amstelland
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
city: Amsterdam
country: Netherlands
facility: Antoni van Leeuwenhoek
city: Apeldoorn
country: Netherlands
facility: Gelre Ziekenhuizen
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Breda
country: Netherlands
facility: Amphia
city: Delft
country: Netherlands
facility: Reinier de Graaf Gasthuis
city: Den Bosch
country: Netherlands
facility: Jeroen Bosch Ziekenhuis
city: Den Haag
country: Netherlands
facility: HagaZiekenhuis
city: Deventer
country: Netherlands
facility: Deventer ziekenhuis
city: Eindhoven
country: Netherlands
facility: Máxima Medisch Centrum
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Goes
country: Netherlands
facility: Admiraal de Ruyter Ziekenhuis
city: Groningen
country: Netherlands
facility: Martini Ziekenhuis
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
city: Leeuwarden
country: Netherlands
facility: Medisch Centrum Leeuwarden
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Maasstad Ziekenhuis
city: Schiedam
country: Netherlands
facility: Franciscus Gasthuis & Vlietland
city: Tilburg
country: Netherlands
facility: Elisabeth-TweeSteden Ziekenhuis
city: Venlo
country: Netherlands
facility: VieCuri Medisch Centrum
Study officials:
affiliation: NKI-AvL
name: Vincent V.O. Dezentjé, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Inge I.R. Konings, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Erasmuc MC
name: Monique M.E.M.M. Bos, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: