Breast cancer
Conditions
Interventions
Alpelisib 300mg once daily (may be reduced to 1dd250 or 1dd200mg in case of
toxicity) + fulvestrant 300mg 1x/four weeks.
Sponsors
BOOG Study Center
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Adult women and men (>= 18 years of age) with proven diagnosis of adenocarcino-ma 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 * Estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer based 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
Exclusion criteria: * Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in the short term * Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progressive growth * Prior treatment with an PI3K /AKT/mTOR inhibitor * Prior treatment with chemotherapy in the advanced setting * (prior) use of oral SERD in any setting * Type 1 diabetes or uncontrolled type 2 diabetes (Hba1C > 68 mmol/mol) * Clinically significant, uncontrolled heart disease and/or recent cardiac events
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - to determine 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
| Measure | Time frame |
|---|---|
| - to determine *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; - 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 determine timing and severity of alpelisib-induced hyperglycaemia; - to determine risk factors for alpelisib-induced hyperglycaemia; - 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 pharmacokinetics of alpelisib. | — |
Countries
Netherlands
Outcome results
None listed