EUCTR2017-002361-22-DE进行中（未招募）1 期
A Phase II, Open Label, Randomised, Multi-centre Study to Assess the Safety and Efficacy of Agents Targeting DNA Damage Repair in Combination with Olaparib versus Olaparib Monotherapy in the Treatment of Metastatic Triple Negative Breast Cancer Patients Stratified by Alterations in Homologous Recombinant Repair (HRR)-related Genes (including BRCA1/2) (VIOLETTE)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,300
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Provision of informed consent prior to any study specific procedures
- •2. Patients must be male or female =18 years of age
- •3. Progressive cancer at the time of study entry
- •4. Histologically or cytologically confirmed TNBC at initial diagnosis with
- •evidence of metastatic or incurable advanced locoregional disease
- •(defined as ER and PgR negative [IHC nuclear staining <1% positive]
- •and HER2 negative [IHC 0, 1+ or IHC 2+ with corresponding ISH nonamplified
- •of ratio less than 2.0 or ISH non-amplified ratio less than 2.0]
- •as per ASCO-CAP HER2 guideline recommendations 2013 (ASCO-CAP).
- •Note: An Allred score of 0-2 is acceptable however for a score of 2 the
- •Proportion score must be checked to make sure it is 1 (=1% cells are ER
- •5. Patients must have received at least 1 and no more than 2 prior lines
- •of treatment for metastatic or incurable advanced locoregional disease
- •with an anthracycline (doxorubicin, epirubicin) and/or a taxane (eg,
- •paclitaxel, docetaxel) unless contraindicated, in either the neo-adjuvant,
- •adjuvant or metastatic setting
- •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
- •Patients who have received prior platinum based chemotherapy are
- •eligible if platinum was given either as potentially curative treatment for
- •a prior non breast cancer (ovarian cancer) with no evidence of disease
- •for =5 years prior to study entry or as adjuvant/neoadjuvant treatment
- •for breast cancer provided at least 12 months have elapsed between the
- •last dose of platinum-based treatment and randomisation
- •6. Confirmed presence of qualifying HRR mutation or absence of any HRR
- •mutation in tumour tissue by the Lynparza HRR assay
- •- FFPE tumour tissue blocks are required for each patient, but if not
- •available, tissue sections are accepted. At least twenty (thirty
- •preferable) unstained sections without cover slips must be submitted to
- •ensure sufficient material for the prospective Lynparza HRR testing to
- •determine study eligibility and research that will aid understanding of
- •the patient population relative to treatment with DDR and other cancer
- •- If a patient has a previously known qualifying BRCA1/2 mutation or
- •other HRR mutation, then the patient can be invited to consent to the full
- •study. The patient will need to consent to provide an archival tumour
- •block or tissue sections for central assessment of the HRR mutation
- •7. At least one measurable lesion that can be accurately assessed at
- •baseline by computed tomography (CT) (magnetic resonance imaging
- •[MRI] where CT is contraindicated) and is suitable for repeated
- •assessment as per RECIST 1.1
- •8. Patients must have normal organ and bone marrow function measured
- •within 28 days prior to randomisation as defined below:
- •a) Haemoglobin =10.0 g/dL with no blood transfusions (packed red
- •blood cells) in the past 28 days
- •b) Absolute neutrophil count = 1.5 x 109 /L
- •c) Platelet count =100 x 109 /L with no platelet transfusions in the past
- •d) Total bilirubin =1.5 x institutional upper limit of normal unless the
- •patient has documented Gilbert's Syndrome
- 另有 4 项未显示
排除标准
- •1.Involvement in the planning and/or conduct of the study (applies to
- •AstraZeneca staff and/or staff at the study site)
- •2.Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy
- •within 21 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy
- •must have been completed 21 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 5 days prior to study treatment
- •3.More than 2 prior lines of cytotoxic chemotherapy for metastatic
- •- 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
- •- Treatment with biologics will not be considered as prior line of therapy
- •4. Previous randomisation in the present study
- •5. Previous treatment with a PARP inhibitor (including olaparib) or other
- •DDR inhibitor (unless treatment was for less than 3 weeks duration and
- •at least 12 months have elapsed between the last dose and
- •randomisation. Patients that did not tolerate prior treatment are
- •6. Exposure to a small molecule IP within 30 days or 5 half-lives
- •(whichever is longer) prior to randomisation. The minimum washout
- •period for immunotherapy shall be 42 days
- •7. Patients with MDS/AML or with features suggestive of MDS/AML
- •8. Patients with second primary cancer, EXCEPTIONS: adequately treated
- •non melanoma 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 curatively treated with no evidence of
- •disease for = 5 years prior to study entry (including lymphomas [without
- •bone marrow involvement])
- •9. Mean resting corrected QTc interval using the Fridericia formula
- •(QTcF) >470 msec/female patients and >450 msec for male patients (as
- •calculated per institutional standards) obtained from 3 ECGs performed
- •2-5 minutes apart at study entry, or congenital long QT syndrome
- •No longer applicable from CSPv6.0 AZD1775 should not be given to
- •patients who have a history of Torsades de pointes unless all risk factors
- •that contributed to Torsades have been corrected. AZD1775 has not been
- •studied in patients with ventricular arrhythmias or recent myocardial
- •10. Any of the following cardiac diseases currently or within the last 6
- •- Unstable angina pectoris
- •- Congestive heart failure = Class 2 as defined by the New York Heart
- •Association
- •- Acute myocardial infarction
- •- Conduction abnormality not controlled with pacemaker or medication
- •(patients with a conduction abnormality controlled with pacemaker or
- •medication at the time of screening are eligible)
- •- Significant ventricular or supraventricular arrhythmias (patients with
- •chronic rate-controlled atrial fibrillation in the absence of other cardiac
- •abnormalities are eligible)
- •11. Concomitant use of known strong cytochrome P (CYP) 3A inhibitors
- 另有 5 项未显示
研究者
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