BOOG 2017-04

General Information

BOOG number

BOOG 2017-04




Date: 01/04/2020

Inclusion closed


Participating parties / group


Full title

A phase II, multicenter, open-label, two-cohort, non-comparative study to assess the efficacy and safety of alpelisib plus fulvestrant or letrozole in patients with PIK3CA mutant, hormone receptor (HR) positive, HER2- negative advanced breast cancer (aBC), who have progressed on or after CDK 4/6 inhibitor treatment




Target sample size

340 (6 in NL)

Actual accrual

340 (6 in NL)
Date: 01/04/2020

Estimated study completion date





Principal Investigator(s)

Prof. Dr V. Tjan-Heijnen

Study manager

Michiel van de Wetering, Novartis

Central datamanagement and randomization




Local datamanagement





Analyses cohort A en B zijn gepresenteerd en gepubliceerd: 1. Rugo HS, et al ASCO 2020. Abstract 1006. 2. Andre F, et al. N Engl J Med 2019 3. Turner S. et al ESMO 2020. Poster 309P 4. Rugo HS, et al SABCS 2020 Alpelisib plus fulvestrant in PIK3CA-mutated, hormone receptor-positive advanced breast cancer after a CDK4/6 inhibitor (BYLieve): one cohort of a phase 2, multicentre, open-label, non-comparative study Prof Hope S Rugo, et al Lancet Oncology DOI:


This is a phase II, multicenter, open-label, two-cohort, non-comparative study of alpelisib plus endocrine therapy (either fulvestrant or letrozole) in patients with HR+, HER2-negative aBC harboring PIK3CA mutation(s) in the tumor whose disease has progressed on or after CDK 4/6 inhibitor containing treatments


The primary objective is to assess the proportion of patients who are alive without disease progression at 6 months based on local investigator assessment per RECIST v1.1 in Cohort A (alpelisib in combination with fulvestrant) and Cohort B (alpelisib in combination letrozole) among patients with HR+, HER2-negative aBC harboring a PIK3CA mutation whose disease had progressed on or after CDK 4/6 inhibitor combination with an AI or fulvestrant. Secondary objectives: – To assess PFS based on local investigator assessment for each cohort  – To assess PFS on next-line treatment (PFS2) for each cohort  – To assess overall response rate (ORR) and clinical benefit rate (CBR) based on local investigator assessment for each cohort  – To assess duration of response (DOR) in patients with confirmed complete response (CR) or partial response (PR) for each cohort  – To evaluate the safety and tolerability of the combination for each cohort


The primary efficacy endpoint is the proportion of patients who are alive without disease progression at 6 months based on local investigator assessment using RECIST v1.1 in each cohort.

Eligibility Criteria

Key Inclusion criteria: Patient is a male or postmenopausal female ≥ 18 years old.  Patient has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory. It is recommended to provide a tumor sample collected after the most recent progression or recurrence  Patient has identified PIK3CA mutant status determined by a Novartis designated laboratory  Patient has a confirmed, HER2-negative aBC. HER2-negative d efined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0, 1+ or 2+.  Patients must be diagnosed with aBC, with documented evidence of progression on or after CDK 4/ 6 inhibitor treatment. Note: CDK 4/6 inhibitor has to be the last treatment regimen prior to study entry. Patients who received one prior chemotherapy for aBC (either in the adjuvant or metastatic setting) are allowed. The maximum number of prior therapies for aBC or mBC is limited to two. Patients must have recovered to grade 1 or better from any adverse events (except alopecia) related to previous therapy prior to study entry. For male patients, prior AI treatment is not required.  Patient has histologically and/ or cytologically confirmed ER+ and/ or PgR+ BC  Patient has either measurable disease i.e., at least one measurable lesion as per RECIST v1.1 criteria or if no measurable disease is present than at least one predominantly lytic bone lesion must be present Patient has ECOG performance status of ≤ 2  Patient has adequate bone marrow function Key Exclusion criteria: Patient has received prior treatment with any PI3K inhibitors  Patient with clinically manifest diabetes mellitus, or documented steroid induced diabetes mellitus  Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer  Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia)  Patients receiving corticosteroids ≤ 2 weeks prior to treatment. at the time of study entry except in cases outlined below:  Bilateral diffuse lymphangitis carcinomatosis  History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis  Patient has impaired GI function or GI disease that may affect the absorption of study drugs  Patient has documented pneumonitis  Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A (Rifabutin, Rifampicin, Clarithromycin, Ketoconazole, Ietroconazole, Voriconazole, Ritinavir, Telithromycin) within the last 5 days prior to study entry

Regulatory Information

CCMO approval

Date: 25/10/2017
Nr: NL61664.068.17

EC approval

Date: 31/01/2018


Academisch Ziekenhuis Maastricht

EudraCT number


Trial Register