An Open-Label, Non-randomized, Prospective Biomarker Study to Assess Analytic Concordance Between Non-invasive Testing and Tissue Testing for EGFR T790M Mutation Detection in Patients With Non-small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- The percentage of patients whose T790M results on Trovera urine AND Guardant360 plasma testing match their T790M results on cobas tissue testing.
研究概览
简要总结
The study is being done to determine if non-invasive testing (urine and plasma testing) is as effective as tissue testing in identifying epidermal growth factor receptor (EGFR) T790M mutation status. EGFR is a type of protein found on the surface of cells in the body. When this protein is mutated and becomes too active, it can lead to cancer growth. T790M is a mutation that develops in response to treatment of the EGFR mutation.
Participating patients will have tumor tissue (via cobas test), as well as 2 plasma samples (via cobas and Guardant360 tests) and 1 urine sample (via Trovera test), tested for EGFR T790M mutation status. If the results of the cobas tissue and/or plasma test show that a patient is T790M positive, they will be treated according to standard of care, which may include treatment with osimertinib. Osimertinib is approved for use in the United States for the treatment of EGFR T790M mutation-positive non-small cell lung cancer (NSCLC).
详细描述
RADIANCE is an open-label, prospective biomarker study to assess analytic concordance between non-invasive testing (plasma and urine) and tissue testing for the EGFR T790M mutation. All patients will have tumor tissue (via cobas test) as well as 2 plasma samples (via cobas and Guardant360) and 1 urine sample (via Trovera) tested for the EGFR T790M mutation (Part 1). Patients who are confirmed T790M negative based on both cobas biomarker tests (tissue and plasma) will have completed the study. Patients who demonstrate T790M+ on cobas tissue and/or cobas plasma testing may choose to undergo treatment with osimertinib in consultation with their healthcare provider (no investigational product will be provided for this study) and will continue to Part 2. In case of insufficient samples for biomarker testing or invalid results from any of the 4 testing modalities, another sample may be acquired from the patient, if feasible, including the patient's decision to undergo a second biopsy. Failure of a patient to undergo a tissue, plasma, or urine sample collection for biomarker testing will result in their withdrawal from the study. If 1 or more samples are insufficient for testing or 1 or more of the test results are invalid, the patient may still qualify for the clinical outcomes part of the study (Part 2) as long as cobas tissue and/or cobas plasma test is T790M+ and the patient receives at least one dose of osimertinib.
During Part 2 Follow-Up Visits will occur according to standard of care, but at least every 12 weeks for the first 12 months of treatment. A Final Study Visit will occur at 18 months (Week 72 +/- 14 days) or upon early withdrawal.
Statistical methods Sample size: The sample size is such to provide enough statistical precision for the primary endpoint. A sample size of 400 patients with evaluable biomarker test results for analytic concordance has been selected in order to achieve a precision of no more than ±5% around the estimated concordance rate. If a 15% inflation factor is applied (~70 patients) to this sample size to take into account those patients who may not be evaluable for concordance estimates, a total of approximately 470 patients will be enrolled.
The Full Analysis Sets will include the following:
Part 1: All patients in the study with cobas tissue, Guardant360 plasma, and Trovera urine test results.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provision of informed consent prior to any study-specific procedures
- •Females and males >/= 18 years
- •Primary diagnosis of NSCLC with evidence of disease progression during or following treatment with an EGFR tyrosine kinase inhibitor (diagnosis of NSCLC that is confirmed by cytology is acceptable)
- •Willing to undergo tumor biopsy (e.g., excision, core biopsy, or endoscopic biopsy), preferably of a progressing lesion, and provide blood and urine for biomarker testing
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
排除标准
- •Involvement in the planning and/or conduct of the study
- •Prior treatment with osimertinib or another T790M directed therapy
- •Current participation in another clinical study with an investigational product or patients who plan to receive any treatment that is not FDA-approved for EGFR mutation positive NSCLC at any time during the course of this study
- •Use of any chemotherapeutic agent within 1 week of tissue, plasma, and urine sample collection
- •For women - currently pregnant or plan to become pregnant during the course of the study: pre-menopausal women of childbearing potential must have a urine or serum pregnancy test performed during the screening/enrollment period and prior to initiating anti-cancer treatment
- •Judgment by the investigator that the patient should not participate in the study due to the patient being unlikely to comply with study procedures, restrictions, and requirements, such as in the case of severe or uncontrolled systemic disease.
研究组 & 干预措施
T790M positive
Patients determined to be T790M positive on cobas tissue and/or cobas plasma testing during Part 1 may be followed for clinical outcomes in Part 2, and will be treated in accordance with standard of care, which may include osimertinib.
干预措施: Other (Drug)
结局指标
主要结局
The percentage of patients whose T790M results on Trovera urine AND Guardant360 plasma testing match their T790M results on cobas tissue testing.
时间窗: Visit 1 (Day-21 to Day 0)
The Overall Percent Agreement will be estimated as analytic concordance between Guardant360 plasma and Trovera urine testing versus cobas tissue testing in identifying T790M status (positive or negative). The Positive Percent Agreement will be estimated as the percentage of cobas tissue positive patients who are also Guardant360 plasma and/or Trovera urine positive. The Negative Percent Agreement will be estimated as the percentage of cobas tissue negative patients who are also Guardant360 plasma and Trovera urine negative.
次要结局
- Objective Response Rate (ORR)(Every 12 weeks for 12 months)
- Duration of Response (DoR)(Every 12 weeks for the first 12 months, then at week 72)
- Progression Free Survival (PFS)(Every 12 weeks for the first 12 months, then at Week 72)