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

Primary Purpose

Neoplasm, Breast, Congenital, Familial and Genetic Disorders

Status
Recruiting
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Alpelisib 150 MG Oral Tablet [Piqray]
Fulvestrant
Sponsored by
Borstkanker Onderzoek Groep
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neoplasm, Breast focused on measuring Hormone receptor positive HER2 negative breast cancer, PIK3CA-activated mutation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Noordwest ZiekenhuisgroepRecruiting
  • Ziekenhuisgroep TwenteRecruiting
  • Meander Medisch CentrumRecruiting
  • Ziekenhuis AmstellandRecruiting
  • Amsterdam UMCRecruiting
  • Antoni van LeeuwenhoekRecruiting
  • Gelre ZiekenhuizenRecruiting
  • RijnstateRecruiting
  • AmphiaRecruiting
  • Reinier de Graaf GasthuisRecruiting
  • Jeroen Bosch ZiekenhuisRecruiting
  • HagaZiekenhuisRecruiting
  • Deventer ziekenhuisRecruiting
  • Máxima Medisch CentrumRecruiting
  • Medisch Spectrum TwenteRecruiting
  • Admiraal de Ruyter ZiekenhuisRecruiting
  • Martini ZiekenhuisRecruiting
  • Spaarne GasthuisRecruiting
  • Medisch Centrum LeeuwardenRecruiting
  • St. Antonius ZiekenhuisRecruiting
  • Canisius Wilhelmina ZiekenhuisRecruiting
  • Maasstad ZiekenhuisRecruiting
  • Franciscus Gasthuis & VlietlandRecruiting
  • Elisabeth-TweeSteden ZiekenhuisRecruiting
  • VieCuri Medisch CentrumRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm A (one-arm study)

Arm Description

Alpelisib plus fulvestrant beyond progression

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

'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
Objective Response Rate
Described as complete response (CR) or partial response (PR)
Clinical Benefit Rate
Described as stable disease (SD), PR, or CR
Duration of Response (DoR)
Duration of Response

Full Information

First Posted
May 16, 2022
Last Updated
October 5, 2023
Sponsor
Borstkanker Onderzoek Groep
Collaborators
Novartis Pharma B.V., BOOG Study Center
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1. Study Identification

Unique Protocol Identification Number
NCT05392608
Brief Title
SEQUence of Endocrine Therapy in Advanced Luminal Breast Cancer (SEQUEL-Breast)
Acronym
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 2, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
March 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Borstkanker Onderzoek Groep
Collaborators
Novartis Pharma B.V., BOOG Study Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasm, Breast, Congenital, Familial and Genetic Disorders
Keywords
Hormone receptor positive HER2 negative breast cancer, PIK3CA-activated mutation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
130 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm A (one-arm study)
Arm Type
Experimental
Arm Description
Alpelisib plus fulvestrant beyond progression
Intervention Type
Drug
Intervention Name(s)
Alpelisib 150 MG Oral Tablet [Piqray]
Other Intervention Name(s)
Piqray
Intervention Description
Alpelisib 300mg once daily (may be reduced to 1dd250 or 1dd200mg in case of toxicity)
Intervention Type
Drug
Intervention Name(s)
Fulvestrant
Other Intervention Name(s)
Faslodex
Intervention Description
Fulvestrant 300mg 1x/four weeks
Primary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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.
Time Frame
From registration to progression, assessed up to 36 months
Secondary Outcome Measure Information:
Title
'On treatment' Progression-free survival (PFS)
Description
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
Time Frame
From registration to progression, assessed up to 36 months
Title
Objective Response Rate
Description
Described as complete response (CR) or partial response (PR)
Time Frame
From registration to progression, assessed up to 36 months
Title
Clinical Benefit Rate
Description
Described as stable disease (SD), PR, or CR
Time Frame
From registration to progression, assessed up to 36 months
Title
Duration of Response (DoR)
Description
Duration of Response
Time Frame
From registration to progression, assessed up to 36 months
Other Pre-specified Outcome Measures:
Title
Determine circulating tumor DNA (ctDNA) in plasma before and during treatment
Description
Exploratory endpoint; determine circulating tumor DNA (ctDNA) in plasma before and during treatment, to investigate the prognostic and possibly predictive values of these measures
Time Frame
At baseline, 2 weeks of treatment, 8 weeks of treatment and every 8 weeks until disease progression. Assessed up to 36 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Annemarie C.A.M. Almekinders, MD
Phone
020 512 2439
Email
sequel@nki.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vincent V.O. Dezentjé, MD PhD
Organizational Affiliation
NKI-AvL
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Inge I.R. Konings, MD PhD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Monique M.E.M.M. Bos, MD PhD
Organizational Affiliation
Erasmuc MC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Noordwest Ziekenhuisgroep
City
Alkmaar
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S. Vrijaldenhoven
Facility Name
Ziekenhuisgroep Twente
City
Almelo
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E Siemerink
Facility Name
Meander Medisch Centrum
City
Amersfoort
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J Baas
Facility Name
Ziekenhuis Amstelland
City
Amstelveen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A van Zweeden
Facility Name
Amsterdam UMC
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
I. Konings
Facility Name
Antoni van Leeuwenhoek
City
Amsterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
V Dezentjé
Facility Name
Gelre Ziekenhuizen
City
Apeldoorn
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
S Hiddink
Facility Name
Rijnstate
City
Arnhem
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
K Beelen
Facility Name
Amphia
City
Breda
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J Heijns
Facility Name
Reinier de Graaf Gasthuis
City
Delft
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
L Mammatas
Facility Name
Jeroen Bosch Ziekenhuis
City
Den Bosch
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J Tol
Facility Name
HagaZiekenhuis
City
Den Haag
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
D. Houtsma
Facility Name
Deventer ziekenhuis
City
Deventer
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
L Kessels
Facility Name
Máxima Medisch Centrum
City
Eindhoven
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M Dercksen
Facility Name
Medisch Spectrum Twente
City
Enschede
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
M. Pleunis-van Empel
Facility Name
Admiraal de Ruyter Ziekenhuis
City
Goes
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
E van Vliet
Facility Name
Martini Ziekenhuis
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A van der Velden
Facility Name
Spaarne Gasthuis
City
Hoofddorp
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A Beeker
Facility Name
Medisch Centrum Leeuwarden
City
Leeuwarden
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
L. Hamming
Facility Name
St. Antonius Ziekenhuis
City
Nieuwegein
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
P. de Jong
Facility Name
Canisius Wilhelmina Ziekenhuis
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
C. Mandigers
Facility Name
Maasstad Ziekenhuis
City
Rotterdam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A. van der Padt-Pruijsten
Facility Name
Franciscus Gasthuis & Vlietland
City
Schiedam
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
H Zuetenhorst
Facility Name
Elisabeth-TweeSteden Ziekenhuis
City
Tilburg
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
J.M.G.H. van Riel
Facility Name
VieCuri Medisch Centrum
City
Venlo
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
A van de Wouw

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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