MATCH Treatment Subprotocol Z1I: Phase II Study of AZD1775 in Patients With Tumors Containing BRCA1 and BRCA2 Mutations
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This phase II MATCH treatment trial identifiesay block the protein tyrosine kinase WEE1 the effects of AZD1775 in patients whose cancer has a genetic change called BRCA mutation. AZD1775 may block a protein called WEE1, which may be needed for growth of cancer cells that express BRCA mutations. Researchers hope to learn if AZD1775 will shrink this type of cancer or stop its growth.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
- •Patients must have mutation in the BRCA1 or BRCA2 gene in the tumor, or another aberration, as determined via the MATCH Master Protocol. Patients with tumor carrying mutations defined as variants of uncertain significance will not qualify
- •Patients with ovarian cancer or HER2 negative, metastatic breast cancer must have received a PARP inhibitor as part of or as one of their prior lines of therapy
- •Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
- •Patients receiving any medications or substances that are inhibitors or inducers of CYP3A4, or CYP3A4 substrates need to be reviewed by the study investigator. Continuation of such medications will be at the discretion of the study investigator. Concomitant use of aprepitant and fosaprepitant is prohibited
- •Patients have hemoglobin (HgB) >= 9 g/dL, which should be done =< 4 weeks prior to registration to treatment step
- •Resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female (as calculated per institutional standards) obtained from electrocardiogram (ECG), prior to enrollment. If resting QTc interval using the Fridericia formula (QTcF) is > 450 msec/male and > 470 msec/female (as calculated per institutional standards), then 2 additional ECGs should be performed 2-5 minutes apart at study entry. In order to be eligible, the mean resting corrected QTc interval using the Fridericia formula (QTcF) should be < 450 msec/male and < 470 msec/female (as calculated per institutional standards)
排除标准
- •Patients must not have known hypersensitivity to AZD1775 or compounds of similar chemical or biologic composition
研究组 & 干预措施
Treatment (adavosertib)
Patients receive adavosertib PO QD on days 1-5 and 8-12 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
干预措施: Adavosertib (Drug)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Tumor assessments occurred at baseline, then every 3 cycles until disease progression, up to 3 years post registration
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.
Objective response rate (ORR)
时间窗: Up to 3 years
ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response: * For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks) * For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks) * For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)
次要结局
- Overall survival (OS)(Assessed every 3 months for =< 2 years and every 6 months for year 3)
- Progression free survival (PFS)(Assessed at baseline, then every 3 cycles until disease progression, up to 3 years post registration)
- 6-month progression-free survival (PFS) rate(From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months)
- Progression free survival (PFS)(From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years)