Studieoverzicht - 2017-04 BYLieve

 
Number 2017-04 BYLieve
Nickname BYLieve
Status Open Date: 01-11-2017
Inclusion closed
Other study number(s)
Participating parties/groups MUMC+
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
Phase and type male & female
Age ≥18
Menopausal status Not applicable
Indication Advanced/metastatic
Subindication HER2- HR+
Target sample size 160 (6 in NL)
Actual accrual 138 (3 in NL) Date: 01-02-2019
Estimated study completion date 10-04-2020
CCMO approval Yes Date: 25-10-2017 Nr: NL61664.068.17
EudraCT nr. 2016-004586-67
Trial Register NCT03056755
METC approval Yes Date: 31-01-2018 METC: Academisch Ziekenhuis Maastricht Nr: METC171096
Amendments Yes Date:
KWF-CKS approval Not applicable Date: Nr:
News item
Website http://www.boogstudycenter.nl , voor patienten: https://www.kanker.nl/trials/943-bylieve-cbyl719x2402-studie-borstkanker-
Sponsor Novartis
Principal Investigator(s) Prof. Dr V. Tjan-Heijnen
Study manager Jeany Rademaker-Lakhai
Central datamanagement and randomization Novartis
Monitoring Novartis
Local datamanagement Novartis
Funding Novartis
Extra

Design:

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

Objectives:

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

Endpoints:

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.

Main 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
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