A feasibility study of niraparib for advanced, BRCA1-like, HER2-negative breast cancer patients
- Conditions
- Breast cancer, advancedMedDRA version: 19.0Level: LLTClassification code 10072737Term: Advanced breast cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-001852-23-NL
- Lead Sponsor
- KI-AV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- Not specified
• 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 < 2.5 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;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9
• 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method