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

Neoplasm, Breast Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05392608
• Other study ID #: BOOG 2021-01 SEQUEL-Breast
• Status: Recruiting
• Phase: Phase 2
• Start date: June 2, 2022
• Est. completion date: March 2028

Study information

• Verified date: October 2023
• Source: Borstkanker Onderzoek Groep
• Contact: Annemarie C.A.M. Almekinders, MD
• Phone: 020 512 2439
• Email: sequel[@]nki.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: March 2028
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Genetic Diseases, Inborn
• Neoplasm, Breast

Intervention

Drug:
• Alpelisib 150 MG Oral Tablet [Piqray]
Alpelisib 300mg once daily (may be reduced to 1dd250 or 1dd200mg in case of toxicity)
• Fulvestrant
Fulvestrant 300mg 1x/four weeks

Locations

Country	Name	City	State
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	Jeroen Bosch Ziekenhuis	Den Bosch
Netherlands	HagaZiekenhuis	Den Haag
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	Elisabeth-TweeSteden Ziekenhuis	Tilburg
Netherlands	VieCuri Medisch Centrum	Venlo

Sponsors (3)

Lead Sponsor	Collaborator
Borstkanker Onderzoek Groep	BOOG Study Center, Novartis Pharma B.V.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Determine circulating tumor DNA (ctDNA) in plasma before and during treatment	Exploratory endpoint; determine circulating tumor DNA (ctDNA) in plasma before and during treatment, to investigate the prognostic and possibly predictive values of these measures	At baseline, 2 weeks of treatment, 8 weeks of treatment and every 8 weeks until disease progression. Assessed up to 36 months
Primary	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	'On treatment' 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 earlier than disease progression	From registration to progression, assessed up to 36 months
Secondary	Objective Response Rate	Described as complete response (CR) or partial response (PR)	From registration to progression, assessed up to 36 months
Secondary	Clinical Benefit Rate	Described as stable disease (SD), PR, or CR	From registration to progression, assessed up to 36 months
Secondary	Duration of Response (DoR)	Duration of Response	From registration to progression, assessed up to 36 months