Studieoverzicht - 2021-02 ZEST

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

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

Primary Outcome Measures  :

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

Secondary Outcome Measures  :

1. Overall survival (OS) [ Time Frame: Up to 8 years ]
2. Time to progression on next anticancer therapy (TTP) [ Time Frame: Up to 8 years ]
3. Distant recurrence-free survival (DRFS) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to 8 years ]

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.

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.

Deelnemende centra: 

Maastricht UMC+

Medisch Centrum Leeuwarden 

Ikazia ziekenhuis

Noordwest Ziekenhuisgroep

Haga ziekenhuis

Isala ziekenhuis 

Infographic voor patiënten (download link)