Breast cancer, advanced MedDRA version: 19.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Niraparib
Product Code: MK-4827
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Niraparib
CAS Number: 1038915-60-4
Other descriptive name: NIRAPARIB
Concentration unit: mg millig
Sponsors
NKI-AVL
Eligibility
Sex/Gender
All
Inclusion criteria
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; • 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. • Fresh frozen primary tumor sample available or metastasis accessible for fresh frozen biopsy; • 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 one prior line 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; • Measureable or evaluable disease according to RECIST 1.1 criteria (appendix 2); • Minimal acceptable safety laboratory values o ANC of = 1.5 x 109 /L o Platelet count of = 150 x 109 /L o Hemoglobin = 10 g/dL (6,21 mmol/L) o Hepatic function as defined by serum bilirubin = 1.5 x ULN, ASAT and ALAT =65 years) yes F.1.3.1 Number of subjects for this age range 9
Exclusion criteria
Exclusion criteria: • Any treatment with investigational drugs within 28 days prior to receiving the first dose of investigational treatment; or within 21 days for standard chemotherapy; or within 14 days for weekly scheduled chemotherapeutic regimens or endocrine therapy; • Patients who have progressed on previous palliative treatment with PARP1-inhibitors, platinum compounds or high dose alkylating agents with autologous stem cell rescue, since preclinical and anecdotal clinical data in breast cancer indicate that these cancers have acquired resistance to PARP-inhibitors based on genetic reversion, epigenetic modifications, or as yet unknown mechanisms. Platinum-sensitive or PARP1-inhibitor-sensitive patients who stopped for reasons other than progression are eligible; • Patients who received high-dose alkylating agents or platinum compounds in the (neo)adjuvant setting, unless these treatments had been received longer than 3 years ago; • Pretreatment not containing an anthracycline and/or taxane, either in the (neo-) adjuvant or metastatic setting received, or if not, then discussed with the patient whether it is justified to forego these treatments; • Women who have a positive pregnancy test (urine/serum) and/or who are breast feeding; • Unreliable contraceptive methods. Women and men enrolled in this trial must agree to use a reliable contraceptive method throughout the study (adequate contraceptive methods are: intra-uterine devices or systems, condom or other barrier contraceptive measures, sterilization and true abstinence: see also 3.5) • Radiotherapy within the last four weeks prior to receiving the first dose of investigational treatment; except 1x8 Gy for pain palliation then a seven days interval should be maintained; • Patients must not have any known history of myelodysplastic syndrome (MDS) or other cytogenetic abnormality associated with MDS • Patients must not have known persistent (> 4 weeks) = Grade 2 toxicity from prior cancer therapy • Patients must not have known = Grade 3 hematological toxicity with the last chemotherapy regimen • Uncontrolled infectious disease or known Human Immunodeficiency Virus HIV-1 or HIV-2 type patients; • Patients with an active hepatitis B or C; • Recent myocardial infarction (< six months) or unstable angina; • Symptomatic brain or leptomeningeal metastases. If adequately treated with resection and/or irradiation and patients are at least four weeks completely free of symptoms of these metastases with or without corticosteroids, patients could be eligible if all other in- and exclusion criteria are obeyed. • Any medical condition not yet specified above that is considered to possibly, probably or definitely interfere with study procedures, including adequate follow-up and compliance and/or would jeopardize safe treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To establish whether niraparib single agent treatment in advanced BRCA1-like, HER2 negative breast cancer patients deserves to be further studied;Secondary Objective: To determine objective response rate (according to RECIST v1.1 (appendix 2)) • To determine duration of response • To determine the clinical benefit rate (CR + PR + SD = 6 months) • To determine median overall survival • To determine safety and tolerability of niraparib single agent for BRCA1-like, HER2-negative, advanced breast cancer patients • Translational studies, e.g. putative resistance markers, like 53BP1 protein expression, XIST gene expression, PARPi-7 and MammaPrint High1/High2 (MP1/2) signatures as biomarkers of response, genetic reversal in the case of a tumor BRCA1-mutation on tumor material obtained before start and again after progression on niraparib, and discovery studies using whole genome NGS, RNAseq etc. ;Primary end point(s): progression-free survival rate at 4 months;Timepoint(s) of evaluation of this end point: 4 months after start treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • objective response rate (according to RECIST v1.1) • duration of response • clinical benefit rate (CR + PR + SD = 6 months) • median overall survival • safety and tolerability ;Timepoint(s) of evaluation of this end point: •At 5 years after last treatment of last included patient | — |
Countries
Netherlands
Contacts
Public ContactProf. Dr. S. C. Linn
NKI-AVL
Outcome results
None listed