Assessment of the Efficacy and Safety of Olaparib Monotherapy Versus Physicians Choice Chemotherapy in the Treatment of Metastatic Breast Cancer Patients With Germline BRCA1/2 Mutations.
- Conditions
- Metastatic Breast CancerTherapeutic area: Diseases [C] - Cancer [C04]MedDRA version: 18.1Level: LLTClassification code 10027475Term: Metastatic breast cancerSystem Organ Class: 100000004864
- Registration Number
- EUCTR2013-005137-20-HU
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 310
1. *Provision of informed consent prior to any study specific procedures
2. *Patients must be male or female .18 years of age
3. *Histologically or cytologically confirmed breast cancer with evidence of metastatic disease
4. Documented mutation in BRCA1 or BRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
5. *Patients must have received treatment with an anthracycline (e.g. doxorubicin, epirubicin) unless contraindicated and a taxane (e.g. paclitaxel, docetaxel) in either an neoadjuvant/adjuvant or metastatic setting.
6. *Patients who have received platinum (cisplatin or carboplatin, either as monotherapy or in combination) for advanced breast cancer are eligible to enter the study provided there has been no evidence of disease progression during the
platinum chemotherapy
7. Patients who have received prior platinum based chemotherapy are eligible if platinum was
given EITHER a) as potentially curative treatment for a prior non-breast cancer (eg ovarian cancer) with no
evidence of disease for = 5 years prior to study entry OR b) as adjuvant/neoadjuvant treatment for breast cancer provided at least 12 months have elapsed between the last dose of platinum-based treatment and randomization.
8. Patients with estrogen and/or progesterone receptor-positive disease must have received and progressed on at least one endocrine therapy (adjuvant or metastatic), or have disease that the treating physician believes to be inappropriate for endocrine therapy
9. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT (MRI where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1.
10. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined below:
. Haemoglobin = 10.0 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days
. Absolute neutrophil count (ANC) = 1.5 x 10 9/L
. Platelet count = 100 x 10 9/L
. Total bilirubin = 1.5 x institutional upper limit of normal
. AST (SGOT)/ALT (SGPT) = 2.5 x institutional upper limit of normal unless liver metastases are present in which case they must be = 5x ULN
. Serum or plasma creatinine = 1.5 x institutional upper limit of normal (ULN)
11. *ECOG performance status 0-1 within 21 days of randomisation
12. *Postmenopausal or hysterectomized; women of childbearing potential are eligible with a negative urine or serum pregnancy test documenting evidence of non-childbearing status. Postmenopausal is defined as any of the following:
- age = 60 years
- age < 60 years and amenorrheic for 1 year or more in the absence of chemotherapy and/or hormonal treatment
- luteinising hormone (LH), follicle stimulating hormone (FSH) and plasma oestradiol levels in the postmenopausal range for women under 60 years of age
- radiation-induced oophorectomy with last menses >1 year ago
- or surgical sterilisation (bilateral oophorectomy)
13. *Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
14. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary tumour if available For inclusion in
a) the optional exploratory genetic research and/or
b) the optional tumour biopsy research, patients must fulfil the follo
1.*Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff/BCA staff and/or staff at the study site).
2. BRCA1 and/or BRCA2 mutations that are considered to be non detrimental (e.g., Variants of uncertain clinical significance” or Variant of unknown significance” or Variant, favour polymorphism” or benign polymorphism” etc.).
3. Cytotoxic chemotherapy or non-hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted. Endocrine therapy must have been discontinued 7 or more days before Cycle 1 Day 1. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 2 weeks prior to study treatment.
4. *Patients with HER2-positive disease (3+ by IHC or ISH amplified > 2.0).
5. *Previous randomisation in the present study.
6. Exposure to an investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
7. *Any previous treatment with a PARP inhibitor, including olaparib.
8. *Patients with second primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid
tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for . 5 years prior to study entry.
9. Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc .470
msec.
10. *Patients cannot have received more than 2 prior lines of cytotoxic chemotherapy for metastatic disease. Prior treatments with hormonal therapy and non-hormonal targeted therapy are allowed and not counted as a prior line of cytotoxic chemotherapy. For the purposes of this protocol, the combination of an aromatase inhibitor and everolimus is not considered cytotoxic chemotherapy.
*Concomitant use of known potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
12. Persistent toxicities (.CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 2 peripheral neuropathy.
13. *Patients with myelodysplastic syndrome/treatment related acute myeloid leukaemia.
14. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
15. *Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV).
16. *Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive bilateral lung disease on High Resolution Computed Tomography scan or any psychiatric disorder that would limit ability to comply with study procedures, and any other medical condition that, in the opinion of the investigator, places the patient at unacceptable risk of toxicity.
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