NCT03182634Unknown2 期
A Multiple Parallel Cohort, Multi-centre Phase IIa Trial Aiming to Provide Proof of Principle Efficacy for Designated Targeted Therapies in Patients With Advanced Breast Cancer Where the Targetable Mutation is Identified Through ctDNA
Institute of Cancer Research, United Kingdom19 个研究点 分布在 1 个国家目标入组 1,150 人开始时间: 2016年12月15日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 1,150
- 试验地点
- 19
- 主要终点
- The primary endpoint for Cohorts A to E is confirmed objective response rate as defined by RECIST v1.1 for each cohort separately
研究概览
简要总结
plasmaMATCH is a multi-centre phase IIa umbrella trial platform consisting of a ctDNA screening component and a therapeutic component. plasmaMATCH aims to assess whether ctDNA screening can be used to detect patient subgroups who will be sensitive to targeted therapies, and will also assess the safety and activity of the targeted treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years old.
- •Histologically confirmed invasive breast carcinoma.
- •Metastatic or recurrent locally advanced breast cancer that is not suitable for treatment with radical or curative intent.
- •Demonstrated progression of disease by radiological assessment or by clinical assessment within the last 6 weeks.
- •Measurable disease by RECIST v1.
- •Patients must have completed at least one prior line of treatment for advanced breast cancer and/or relapse within 12 months of completing (neo)adjuvant chemotherapy. Patients with HER2 positive breast cancer must have been treated with at least two courses of HER2 targeted therapy in the advanced setting (or one course if no further courses of HER2 targeted therapy are available locally).
- •Patient must either be suitable for a baseline biopsy of recurrent disease or have an archival biopsy of recurrent disease available. Patients are requested to consent to a baseline biopsy but if deemed unsafe by the Investigator, an archival biopsy of recurrent disease can be used instead. If it is deemed unsafe to proceed with baseline biopsy, and no archival recurrent disease biopsy is available, the patient will not be eligible for entry into the treatment cohort.
- •ECOG performance status ≤
- •Life expectancy >3 months in Cohorts A-D, >16 weeks in Cohort E.
- •Patients must be a) surgically sterile; b) have a sterilised sole partner; c) be postmenopausal; d) must agree to practice true abstinence; or e) must agree to use effective contraception during the period of trial treatment and be willing to do so for 6 months following the end of trial treatment. Effective contraception is defined as double barrier contraception (e.g. condom plus spermicide in combination with a diaphragm, cervical cap or intrauterine device). Ovarian suppression with an LHRH agonist is not a method of contraception.
- •Patients of childbearing potential should have a negative serum pregnancy test within 14 days prior to initiation of trial treatment.
- •At least 4 weeks washout period after the end of trial treatment on a different cohort within plasmaMATCH.
- •Adequate haematological, renal and hepatic function as defined by cohort-specific criteria in protocol.
- •For patients with ER positive breast cancer in Cohorts A, B and C: EITHER postmenopausal, as defined by at least one of the following criteria: Age >60 years; Age <60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and serum estradiol and follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females; Documented bilateral oophorectomy; medically confirmed ovarian failure. OR Pre-/peri-menopausal (i.e. not meeting the criteria for being postmenopausal) if being treated with an LHRH agonist that was commenced at least 4 weeks prior to Cycle 1 Day 1, and continues on the LHRH agonist throughout the trial period.
- •NB. Additional eligibility criteria apply for entry into each treatment cohort.
排除标准
- •Prior treatment with radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy, chemotherapy or IMPs during the previous 4 weeks (6 weeks for nitrosoureas, Mitomycin-C) before trial treatment, except for hormonal therapy with LHRH analogues, which are permitted, and bisphosphonates or RANK ligand antibodies that are permitted for the management of bone metastases.
- •Uncontrolled CNS disease (brain metastases or leptomeningeal disease). Patients with prior diagnosis of CNS metastases must be stable by clinical assessment having ceased steroids after prior treatment.
- •History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction within the last 6 months or ventricular arrhythmia. Patients with a history of any of the above listed cardiac conditions judged not to be clinically significant by the local investigator must be notified to the trial team at the ICR-CTSU for approval by the CI and/or Cohort Lead.
- •Ongoing toxic manifestations of previous treatments Grade ≥
- •Exceptions to this are alopecia or toxicities which in the opinion of the Investigator should not exclude the patient. Such cases should be clearly documented in the patient's notes by the Investigator.
- •Major surgery (excluding minor procedures, e.g. placement of vascular access) within 4 weeks of the first dose of trial treatment.
- •Pregnant or breastfeeding.
- •Any condition that according to the treating physician may compromise the patient's safety or the conduct of the trial.
- •Current malignancies of other types, with the exception of adequately treated in situ carcinoma of the cervix and basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy and have no evidence of the disease for 3 years or more are eligible for the trial.
- •NB. Additional eligibility criteria apply for entry into each treatment cohort.
研究组 & 干预措施
Cohort A - Extended-dose fulvestrant
Experimental
Fulvestrant 500mg IM on Cycle 1 Days 1, 8 and 15 and Cycle 2 onwards Days 1 and 15
干预措施: Fulvestrant (Drug)
Cohort B - Neratinib
Experimental
Neratinib 240mg PO on a continuous schedule starting on Cycle 1 Day 1 AND in ER positive breast cancer, fulvestrant 500mg IM on Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1
干预措施: Fulvestrant (Drug)
Cohort B - Neratinib
Experimental
Neratinib 240mg PO on a continuous schedule starting on Cycle 1 Day 1 AND in ER positive breast cancer, fulvestrant 500mg IM on Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1
干预措施: Neratinib (Drug)
Cohort C - AZD5363 and fulvestrant
Experimental
AZD5363 400mg PO BID on a 7 day schedule of 4 days on treatment followed by 3 days off treatment AND fulvestrant 500mg IM Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1
干预措施: Fulvestrant (Drug)
Cohort C - AZD5363 and fulvestrant
Experimental
AZD5363 400mg PO BID on a 7 day schedule of 4 days on treatment followed by 3 days off treatment AND fulvestrant 500mg IM Cycle 1 Days 1 and 15 and Cycle 2 onwards Day 1
干预措施: AZD5363 (Drug)
Cohort D - AZD5363
Experimental
AZD5363 480mg PO BID on a 7 day schedule of 4 days on treatment followed by 3 days off treatment
干预措施: AZD5363 (Drug)
Cohort E - olaparib and AZD6738
Experimental
AZD6738 160mg to be administered once daily on Days 1-7 of each cycle and olaparib 300mg to be administered twice daily on a continuous schedule starting on Cycle 1 Day 1.
干预措施: Olaparib (Drug)
Cohort E - olaparib and AZD6738
Experimental
AZD6738 160mg to be administered once daily on Days 1-7 of each cycle and olaparib 300mg to be administered twice daily on a continuous schedule starting on Cycle 1 Day 1.
干预措施: AZD6738 (Drug)
结局指标
主要结局
The primary endpoint for Cohorts A to E is confirmed objective response rate as defined by RECIST v1.1 for each cohort separately
时间窗: up to 24 weeks
次要结局
- Frequency of mutations identified in ctDNA screening(Baseline)
- Progression free survival(up to 24 weeks)
- Incidence of treatment-emergent adverse events (safety and tolerability)(through study completion, estimated average 1 year)
- Clinical benefit rate(up to 24 weeks)
- Duration of response for each cohort(through study completion, estimated average 1 year)
- The proportion of patients with a targetable mutation who enter a therapeutic component(Baseline)
- Agreement between ctDNA mutation status and tissue mutation status for patients entering the therapeutic component(Baseline)
- Maximum Plasma Concentration (Cmax)(Monthly up to 4 months)
- Area Under the Curve (AUC)(Monthly up to 4 months)
研究者
研究点 (19)
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