Studieoverzicht - 2021-01 SEQUEL-Breast

 
Number 2021-01 SEQUEL-Breast
Nickname SEQUEL-Breast
Status In preparation Date: 28-06-2021
Inclusion closed
Other study number(s)
Participating parties/groups
Full 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
Phase and type Non-randomized Phase II
Age ≥ 18 years
Menopausal status Both pre- and postmenopausal
Indication Advanced/metastatic
Subindication HER2- HR+
Target sample size 105-130
Actual accrual Date:
Estimated study completion date
CCMO approval Date: Nr:
EudraCT nr.
Trial Register
METC approval Date: METC: Nr:
Amendments Date:
KWF-CKS approval Date: Nr:
News item
Website
Sponsor BOOG
Principal Investigator(s) Dr. V.O. Dezentjé (NKI-AvL), Dr. I.R.H.M. Konings (Amsterdam UMC) en Dr. M.M.E.M. Bos (ErasmusMC)
Study manager Dr. S.M. van den Berg (BOOG Study Center)

Studycoördinator:
C.A.M. Almekinders
c.almekinders@nki.nl
020-512 2439
Central datamanagement and randomization NKI Data Center
Monitoring NKI Data Center
Local datamanagement Centrum zelf of IKNL
Funding Novartis
Extra

Design:

Multicenter, single arm phase II trial

Objectives:

To investigate the efficacy of the combination of fulvestrant and alpelisib directly after progression on 1st or 2nd line therapy with fulvestrant in patients pretreated with a CDK 4/6 inhibitor (in first or second line) in pre- or postmenopausal women and men with HR+HER2- advanced breast cancer with tumors harboring an activating PIK3CA mutation. Primary endpoint is PFS. The aim is to determine a clinically meaningful median PFS of at least six months.

 

Endpoints:

Primary endpoint:

To determine ‘complete’ 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 endpoints:

- to determine Progression-free survival (PFS) ‘on treatment’, 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;

- to determine the Objective Response Rate, described as complete response (CR) or partial response (PR);

- to determine the Clinical Benefit Rate, described as stable disease (SD), PR, or CR;

- to determine the Duration of Response (DoR);

- to evaluate safety and tolerability;

- to assess Quality of Life (QoL);

- to evaluate Patient Reported Outcome Measures (PROMs);

- to compare PFS in patients with the 11 most frequent activating PIK3CA mutations with PFS in patients with unselected activating PIK3CA mutations (including rare mutations);

- to determine Overall Survival (OS);

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

- to explore mechanisms of resistance using tumor DNA and ctDNA;

- to determine pharmacokinetics of alpelisib.

Main eligibility criteria:

The most important inclusion criteria are:  

1. Adult women (≥ 18 years of age) and men with proven diagnosis of adenocarcinoma of the breast with locoregional recurrent or metastatic disease not amenable to resection or radiation therapy with curative intent and for whom chemotherapy is not clinically indicated.

2. Documentation of histologically or cytologically confirmed diagnosis of estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer based on local laboratory results. In case ER ≤ 10% and PR >10% the ER and PR expression need to be confirmed in a referral center. Tumor must be HER2-negative as defined by ASCO-CAP guidelines. If HER2 status is unavailable then testing must be performed/repeated.

3. Patients must have progressed on fulvestrant as a preceding treatment line (as first or second line therapy). In case fulvestrant plus a CDK4/6 inhibitor has been given in 1st line as last treatment, the patient must have progressed during or shortly (<12 months) after stopping adjuvant treatment with an (NS)AI.

4. Previous treatment with a CDK4/6 inhibitor in the advanced setting is mandatory.

5. The presence of an activating PIK3CA mutation; preferably detected in a metastasis as PIK3CA mutation status may change during the course of the disease. In case a biopsy from a metastasis is not obtainable, mutation analysis may be performed on the primary tumor or archival tumor material.

6. Evaluable disease* as defined per RECIST v.1.1. Tumor lesions previously irradiated or subjected to other locoregional therapy will only be deemed measurable if disease progression at the treated site after completion of therapy is clearly documented.

* Evaluable disease in this study is defined as measurable and non-measurable disease according to RECIST, with the exception of truly non-measurable disease only (i.e. ascites or pleural effusion as only site of disease). In case of truly non-measurable disease only, a patient is NOT considered evaluable according to RECIST. Bone only disease is considered evaluable.

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