Zoek
Inloggen

ZEST

  • Active, not recruiting

BOOG 2021-02

General Information

BOOG number

BOOG 2021-02

Nickname

ZEST

Status

  • Active, not recruiting
Date: 25/04/2023

Inclusion closed

25/04/2023

Participating parties / group

GlaxoSmithKline

Other study number

213831

Full title

A Randomized Phase 3 Double-Blinded Study Comparing the Efficacy and Safety of Niraparib to Placebo in Participants With Either HER2-Negative BRCA-Mutated or Triple-Negative Breast Cancer With Molecular Disease Based on Presence of Circulating Tumor DNA After Definitive Therapy

Indication

  • Adjuvant

Subindication

HER2-, any HR

Description

Niraparib treatment based on the presence of ctDNA

Target sample size

800 (global)

Actual accrual

NL: 2 Global: 35
Date: 24/03/2023

Estimated study completion date

31/05/2029

Number of active sites

6

Contact

Sponsor

GlaxoSmithKline

Study manager

Dr. A.E. van Leeuwen-Stok (BOOG Study Center)

Central datamanagement and randomization

GlaxoSmithKline

Monitoring

GlaxoSmithKline

Funding

GlaxoSmithKline

Other

De ZEST studie is vroegtijdig gesloten voor deelname. De reden voor het besluit is dat het aantal patiënten waarbij er circulerend tumor DNA in het bloed werd gevonden veel lager was dan verwacht en er was een veel hoger percentage patiënten dan verwacht met een ctDNA-positieve test die ook al radiologisch detecteerbare ziekte vertoonden tijdens screening. Daardoor is de studie niet haalbaar gebleken. De studie is niet gestopt om redenen van veiligheid of werkzaamheid.

Patiënten die reeds geincludeerd zijn hebben de gelegenheid om hun behandeling met niraparib voort te zetten. Ook zullen er uitgebreide analyse volgen uit de verzamelde data van alle gescreende patiënten.

Design

A Randomized multicenter, double-blinded, placebo-controlled phase 3 study

Participating sites

  • Maastricht UMC+
  • Medisch Centrum Leeuwarden
  • Ikazia ziekenhuis
  • Noordwest Ziekenhuisgroep
  • Haga ziekenhuis
  • Isala ziekenhuis

Objectives

Evaluation of the efficacy of niraparib relative to placebo as measured by progression-free survival (PFS)

Endpoints

Primary Outcome Measures:

  1. Disease-free survival (DFS) [TimeFrame:Up to 4 years]

 

Secondary Outcome Measures:

  1. Overall survival (OS) [TimeFrame:Up to 8 years]
  2. Time to progression on next anticancer therapy (TTP) [TimeFrame:Up to 8 years]
  3. Distant recurrence-free survival (DRFS) [TimeFrame:Up to 4 years]
  4. Number of participants with Treatment-emergent adverse events (TEAEs), Serious adverse events (SAEs), TEAEs leading to death, and AEs leading to discontinuation [TimeFrame:Up to 8 years]
  5. Number of participants with clinically significant changes in laboratory parameters, vital signs, Eastern Cooperative Oncology Group (ECOG) status, physical examination and use of concomitant medications [TimeFrame:Up to 8 years]
  6. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) (Scores on a scale) [TimeFrame:Baseline (Day 1) and up to 8 years]
  7. Change from Baseline in the Functional Assessment of Cancer Therapy – General Population(FACT-GP5) (Scores on a scale) [TimeFrame:Baseline (Day 1) and up to 8 years]
  8. Patient reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) (Scores on a scale) [TimeFrame:Up to 8 years]

Eligibility Criteria

Inclusion Criteria:

  • Stage I to III breast cancer with surgical resection of the primary tumor that is confirmed to be either: TNBC, irrespective of BRCA status or HR+/HER2- breast cancer with a known and documented tBRCA mutation.
  • Completed prior standard therapy for curative intent including all of the following, if indicated: neoadjuvant treatment, surgery, adjuvant radiotherapy, and adjuvant chemotherapy.
  • Participants with HR+ breast cancer must be on a stable regimen of endocrine therapy, if indicated, for at least 3 months prior to enrollment. Ovarian suppression, if indicated, must also have been started at least 3 months prior to enrollment.
  • Detectable ctDNA as measured by central Signatera testing. An archival tumor tissue specimen of the primary tumor sufficient in quality and quantity for ctDNA assay design and tBRCA and Homologous recombination deficiency (HRD).

 

Exclusion Criteria:

  • Prior treatment with a Poly Adenosine-diphosphate Ribose Polymerase (PARP) inhibitor.
  • Current treatment with a Cyclin-dependent kinase (CDK)4/6 inhibitor or endocrine therapy other than anastrozole, letrozole, exemestane, and tamoxifen.
  • Participants have any sign of metastasis or local recurrence after comprehensive assessment conducted per protocol.
  • Participants have shown no definitive response to preoperative chemotherapy by pathologic or radiographic evaluation, in cases where preoperative chemotherapy was administered.

Regulatory Information

CCMO approval

Yes
Date: 21/04/2021

EC approval

Yes
Date: 06/07/2021
Amendments:
Yes
Date Last Amendment: 12/02/2024

EudraCT number

2020-003973-23

Downloads

Inloggen