SEQUEL-Breast: a phase 2 study on the combination of alpelisib and fulvestrant after progression on previous therapy with fulvestrant in patients with PIK3CA-mutated, hormone-receptor positive, HER2 negative advanced breast cancer

Phase 1

• Conditions: PIK3CA-mutated, hormone-receptor positive HER2 negative advanced breast cancer; MedDRA version: 24.0Level: PTClassification code 10085481Term: Hormone receptor positive HER2 negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 23.0Level: PTClassification code 10081234Term: PIK3CA-activated mutationSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-004191-33-NL
• Lead Sponsor: BOOG Study Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-03-18
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Adult women and men (= 18 years of age) 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. Estrogen receptor (ER) expression >10% and/or progesterone receptor (PR) expression >10% breast cancer.
3. Patients must have progressed on fulvestrant as a preceding treatment line (as first or second line therapy).
4. Previous treatment with a CDK4/6 inhibitor in the advanced setting.
5. The presence of an activating PIK3CA mutation.
6. Evaluable disease as defined per RECIST v.1.1.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Patients with advanced, symptomatic, visceral spread, who are at risk of life-threatening complications in the short term (visceral crisis).
2. Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or progres-sive growth.
3. Prior treatment with a PI3K /AKT/mTOR inhibitor.
4. Type 1 diabetes or uncontrolled type 2 diabetes (Hba1C at screening exceeds 68 mmol/mol).
5. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection.
6. Clinically significant, uncontrolled heart disease and/or recent cardiac events.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy of the combination of fulvestrant and alpelisib directly after progression on 1st or 2nd line therapy with fulvestrant (monotherapy or in combination with a CDK 4/6 inhibitor) in pre- or postmenopausal women and men with HR+HER2- advanced breast cancer with tumors harboring an activating PIK3CA mutation. Previous treatment with a CDK 4/6 inhibitor (either in 1st or 2nd line) is mandatory. ;Secondary Objective: Not applicable;Primary end point(s): - 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.;Timepoint(s) of evaluation of this end point: Final analysis