A feasibility study of niraparib for advanced, BRCA1-like, HER2-negative breast cancer patients: the ABC study

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 39

Inclusion Criteria

* Histological proof of advanced, HER2 negative breast cancer;
* The tumor must be BRCA1-like, as identified by Agendia*s RNA-based BRCAness
classifier;with a maximum of 25% of the study population in each stage.
* Only the following patients may be referred for BRCA1-like testing: all
patients that had triple negative primary breast cancer; hormone-receptor
positive, HER2-negative primary breast cancer patients with a histological
grade III breast cancer; Breast cancer patients carrying a BRCA1 and/or BRCA2
germ line mutation.
* Pretreatment containing an anthracycline and/or taxane in the (neo-)adjuvant
or metastatic setting received, or if not, then discussed with the patient
whether it is justified to forego these treatments;
* Maximum of two prior lines of chemotherapy for advanced disease.
* Age * 18 years;
* Able and willing to give written informed consent;
* WHO performance status of 0, 1 or 2;
* Life expectancy * 3 months, allowing adequate follow up of toxicity
evaluation and antitumor activity;
* Measurable or evaluable disease according to RECIST 1.1 criteria;
* Minimal acceptable safety laboratory values
-ANC of * 1.5 x 109 /L
-Platelet count of * 150 x 109 /L
-Hemoglobin * 10 g/dL (6.21mmol/L)
-Hepatic function as defined by serum bilirubin * 1.5 x ULN, ASAT and ALAT <
2.5 x ULN; Subjects who have obligatory liver toxic medication or liver
steatosis should have values < 5 x ULN.
* Renal function as defined by serum creatinine * 1.5 x ULN or creatinine
clearance * 50 mL/min (by Cockcroft-Gault formula);
* Negative pregnancy test (urine/serum) for female patients with childbearing
potential.

Exclusion Criteria

* Any systemic anticancer treatment within 14 days prior to receiving the first
dose of investigational treatment; , except for endocrine therapy that may be
continued up to 1 week before start niraparib
* Patienten met progressive op eerdere palliatieve behandeling met
PARP1-remmers, platina bevattende behandeling of hoge dosis alkylerende
middelen met stam cel transplanatatie.
Platinum-gevoelige of PARP1-remmer-gevoelige patienten die om andere reden dan
progressive zijn gestopt zijn wel eligible;
* Patienten die hoge dosis alkylerende midelen met autologe stam cel
transplantatie hebben gehad in (neo)adjuvante setting, tenzij deze behandleing
meer dan 3 jaar geleden is gegeven;
*Voorbehandeling bevat geen anthracycline en/of taxane, in de (neo-) adjuvante
of gemetastaseerde setting tenzij deze behandelingen gecontraindiceerd zijn;

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Progression-free survival rate at 4 months (PFSR-4m) as assessed according to<br /><br>RECIST v1.1</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* To determine objective response rate (according to RECIST v1.1)<br /><br>* To determine duration of response<br /><br>* To determine the clinical benefit rate (CR + PR + SD * 6 months)<br /><br>* To determine median overall survival<br /><br>* To determine safety and tolerability of niraparib single agent for<br /><br>BRCA1-like, HER2-negative, advanced breast cancer patients<br /><br>* Translational studies, e.g. putative resistance markers, like ex vivo RAD51<br /><br>assay, 53BP1 protein expression, XIST gene expression, genetic reversal in the<br /><br>case of a tumor BRCA1-mutation on tumor material obtained before start and<br /><br>again after progression on niraparib, and discovery studies using whole genome<br /><br>NGS, RNAseq etc.</p><br>

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