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The study is being done to determine if non-invasive testing (urine and blood 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 as well as blood and urine samples, tested for EGFR T790M mutation status. If the results of one of the three tests 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).
The study will look at how well patients who are confirmed T790M mutation positive (by urine and blood testing) respond to treatment compared to patients who are confirmed T790M positive by tissue testing.
RADIANCE is an open-label, prospective biomarker study to assess analytic concordance and clinical validity between non-invasive testing (plasma and urine) and tissue testing for the EGFR T790M mutation. All patients will have tumor tissue as well as plasma and urine samples tested for the EGFR T790M mutation (Part 1). Patients who are confirmed T790M negative based on all 3 biomarker tests; fail to provide sufficient tissue, plasma, and urine samples; yield invalid results for all 3 biomarker tests; or have any combination thereof will be withdrawn from the study. Patients who are T790M+ on at least 1 of the 3 biomarker tests will be treated according to standard of care, as determined by the patient's healthcare provider (no investigational drugs will be provided for this study). Those patients who choose to receive osimertinib treatment and/or are tissue discordant, defined as tissue negative but either plasma or urine positive, will be assessed for clinical outcomes (Part 2) regardless of cancer therapy. If 1 or more of the samples are insufficient for testing or 1 or more of the test results are invalid, the patient may still qualify for Part 2 as long as at least 1 of the 3 biomarker tests is T790M+.
It is expected that ~85% of patients who test positive will elect to receive osimertinib since it is currently the only Food and Drug Administration-approved EGFR tyrosine kinase inhibitor (TKI) that specifically targets T790M in this patient population and represents current treatment distribution estimates. All patients will be tested for the EGFR T790M mutation using tissue, plasma, and urine collected during the Screening/Enrollment Period. Patients who are confirmed T790M negative based on all 3 biomarker tests; fail to provide sufficient tissue, plasma, and urine samples; yield invalid results for all 3 biomarker tests; or have any combination thereof will be withdrawn from the study. Patients who are T790M+ on at least 1 of the 3 biomarker tests will be treated according to standard of care, as determined by the patient's healthcare provider (no investigational drugs will be provided for this study). Those patients who choose to receive osimertinib treatment and/or are tissue discordant, defined as tissue negative but either plasma or urine positive, will be assessed for clinical outcomes (Part 2) regardless of cancer therapy. If 1 or more of the samples are insufficient for testing or 1 or more of the test results are invalid, the patient may still qualify for Part 2 as long as at least 1 of the 3 biomarker tests is T790M+. Follow-Up Visits will occur every 8 weeks for the first 6 months (Weeks 8, 16, and 24) and then every 12 weeks for the second 6 months (Weeks 36 and 48). A Final Study Visit will occur at 18 months (Week 72) or upon early withdrawal. If the EGFR T790M mutation is confirmed by tissue, plasma, or urine test results, treatment options will be discussed with the patient. These standard of care options may include osimertinib. The patient may choose to undergo treatment with osimertinib with the medical guidance of their healthcare provider. It is anticipated that approximately 85% of patients who are T790M+ will receive osimertinib (recommended dose of 80 mg once per day, administered orally) because it is currently the only EGFR TKI that specifically targets T790M in this patient population and represents current treatment distribution estimates, and they will be assessed for clinical outcomes. The remaining 15% of T790M+ patients who do not receive osimertinib will likely receive either chemotherapy or approved checkpoint inhibitors; however, these patients will only be assessed for clinical outcomes if they are tissue discordant, defined as tissue negative but either plasma or urine positive. If patients do receive treatment with osimertinib, osimertinib-related adverse event data will be collected.
Statistical methods Sample size: The sample size is not based on any particular formal hypothesis testing but on the precision of both co-primary endpoints and the key secondary 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. Assuming 60% of the 400 patients evaluable for analytic concordance (240 patients) and 60% of the 70 patients not evaluable for analytic concordance (40 patients) are T790M+ on at least 1 of the 3 biomarker tests, approximately 280 patients will be eligible for follow-up (i.e., Part 2). Approximately 85% (~238 patients) will receive osimertinib for inclusion in the analysis of the co-primary endpoint (objective response rate [ORR]) and secondary endpoints of progression free survival (PFS) and duration of response (DoR). The key secondary endpoint (ORR) will be assessed among discordant cases, defined as tissue negative but either plasma or urine positive, regardless of cancer therapy (~56 patients). Efficacy analysis sets: The Full Analysis Sets will include the following: Part 1: All patients in the study with tissue, plasma, and urine test results. Part 2: The co-primary endpoint (ORR) and secondary endpoints of PFS and DoR will be determined for patients who are T790M+ on at least 1 of the 3 biomarker tests and were treated with at least 1 dose of osimertinib. The key secondary endpoint (ORR) will be assessed among discordant cases (defined as tissue negative but either plasma or urine positive) regardless of cancer therapy.
Safety analysis sets: The safety analysis sets will include the following:
Part 1: All patients in the study from the time of informed consent until the first T790M+ test result is shared with the patient or all 3 biomarker test results are shared with the patient (whichever occurs first). Part 2: Patients who are T790M+ on at least 1 of the 3 biomarker tests (i.e., qualification for the clinical outcomes part of the study) and received at least
1 dose of osimertinib. The analyses of the data collected within this study will be descriptive only, with no formal statistical testing. Continuous variables will be summarized by the number of observations, mean, standard deviation, median, minimum, and maximum. Categorical variables will be summarized by frequency counts and percentages for each category. A Statistical Analysis Plan will be prepared and finalized prior to the first interim analysis, which will occur upon completion of the diagnostic analytic validity part of the study (Part 1). The concordance rate between non-invasive testing and tissue testing will be presented as the point estimate together with the exact 95% confidence interval (CI) estimated using the Clopper-Pearson method. The ORR (co-primary and key secondary endpoints) will also be presented as the point estimate together with the exact 95% CI according to the Clopper-Pearson method.
Duration of response and PFS will be summarized using the Kaplan-Meier (K-M) method with associated K-M curves. The median DoR and PFS will be presented, as well as the rates at clinically relevant time points, together with the associated 95% CIs.
Non-small Cell Lung Cancer
St. Joseph Health
Not yet recruiting
Published on BioPortfolio: 2017-05-03T11:23:43-0400
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