Resistance & Activating Mutations Diagnosed Among NSCLC Community Dwelling EGFR Mutation Positive Patients (RADIANCE)

November 6, 2019 updated by: AstraZeneca

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Part 2: Patients who demonstrate T790M+ cobas tissue and/or cobas plasma testing and were treated with at least 1 dose of osimertinib (i.e., all patients in Part 2).

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 completion of Part 1.

Part 2: Patients who demonstrate T790M+ cobas tissue and/or cobas plasms testing and were treated with at least 1 dose of osimertinib (i.e., all patients in Part 2).

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 cobas 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 will be presented as the point estimate together with the exact 95% CI according to the Clopper-Pearson method. The duration of response (DoR) and progression-free survival (PFS) will be presented for all patients in Part 2, 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.

Study Type

Observational

Enrollment (Actual)

44

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Research Site
    • Ontario
      • Newmarket, Ontario, Canada, L3Y 2P9
        • Research Site
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Research Site
  • United States
    • California
      • Anaheim, California, United States, 92801
        • Research Site
      • Los Angeles, California, United States, 90017
        • Research Site
      • Saint Helena, California, United States, 94574
        • Research Site
      • Santa Rosa, California, United States, 95403
        • Research Site
    • Florida
      • Deerfield Beach, Florida, United States, 33442
        • Research Site
      • Fort Lauderdale, Florida, United States, 33308
        • Research Site
    • Hawaii
      • Honolulu, Hawaii, United States, 96819
        • Research Site
    • Idaho
      • Boise, Idaho, United States, 83706
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Research Site
      • Harvey, Illinois, United States, 60426
        • Research Site
    • Maryland
      • Annapolis, Maryland, United States, 21401
        • Research Site
    • Michigan
      • Southfield, Michigan, United States, 48075
        • Research Site
    • New Jersey
      • Brick, New Jersey, United States, 08724
        • Research Site
    • New Mexico
      • Farmington, New Mexico, United States, 87401
        • Research Site
    • New York
      • White Plains, New York, United States, 10601
        • Research Site
    • North Carolina
      • Asheville, North Carolina, United States, 28801
        • Research Site
      • Hendersonville, North Carolina, United States, 28792
        • Research Site
    • Ohio
      • Kettering, Ohio, United States, 45409
        • Research Site
    • Washington
      • Seattle, Washington, United States, 98109
        • Research Site
      • Seattle, Washington, United States, 98101
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 130 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

The study population for this trial is non-small cell lung cancer patients who will come primarily from the community oncology practice setting.

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Drug: Other
Patients who are T790M positive via cobas plasma and/or cobas tissue testing during Part 1 will be treated per standard of care during Part 2, which may include osimertinib.
Other Names:
  • Standard of Care
T790M negative
Patients determined to be T790M negative during Part 1 will not be followed for clinical outcomes in Part 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The percentage of patients whose T790M results on Trovera urine AND Guardant360 plasma testing match their T790M results on cobas tissue testing.
Time Frame: 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.
Visit 1 (Day-21 to Day 0)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR)
Time Frame: Every 12 weeks for 12 months
The number of patients achieving a confirmed partial response or complete response per RECIST 1.1 from treatment with osimertinib.
Every 12 weeks for 12 months
Duration of Response (DoR)
Time Frame: Every 12 weeks for the first 12 months, then at week 72
The time from first documented tumor response defined by RECIST 1.1 from osimertinib treatment until the date of documented progression or death from any cause.
Every 12 weeks for the first 12 months, then at week 72
Progression Free Survival (PFS)
Time Frame: Every 12 weeks for the first 12 months, then at Week 72
Defined as the time from date of first dose of osimertinib until the date of disease progression by RECIST 1.1 or death by any cause.
Every 12 weeks for the first 12 months, then at Week 72

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of procedure-related adverse events and Serious Adverse Events (SAEs)
Time Frame: Up to 8 weeks after Visit 1
To evaluate safety and tolerability of study procedures.
Up to 8 weeks after Visit 1
Percentage of patients whose Trovera urine OR Guardant360 plasma T790M results are the same as their cobas tissue T790M results.
Time Frame: Visit 1 (Day -21 to Day 0)
The overall percent agreement will be estimate as analytic concordance between cobas tissue and Guardant360 plasma, and cobas tissue and Trovera urine testing in identifying T790M status. The positive percent agreement will be estimated as the percentage of cobas tissue positive patients who are also Guardant360 plasma positive and cobas tissue positive patients who are Trovera urine positive. The negative percent agreement will be estimated as the percentage of cobas tissue negative patients who are also Guardant360 plasma negative and cobas tissue negative patients who are Trovera urine negative.
Visit 1 (Day -21 to Day 0)
The presence of additional biomarkers from the blood and/or urine of NSCLC patients who have progressed during or following treatment with an EGFR tyrosine kinase inhibitor
Time Frame: Visit 1 (Day -21 to Day 0)
Biomarker results will be assessed and may be compared to T790M status and/or clinical response.
Visit 1 (Day -21 to Day 0)
Percentage of patients whose Trovera urine OR Guardant360 plasma EGFR mutation results are the same as their cobas tissue EGFR mutation results.
Time Frame: Visit 1 (Day -21 to Day 0)
The overall percent agreement will be estimated as analytic concordance between Guardany360 plasma and Trovera urine testing versus cobas tissue testing in identifying the status of specified EGFR mutations. 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.
Visit 1 (Day -21 to Day 0)
Physical Exam
Time Frame: Up to 8 weeks after Visit 1
Changes in physical exams from baseline
Up to 8 weeks after Visit 1
Vital signs
Time Frame: Up to 8 weeks after Visit 1
Changes in vital signs from baseline
Up to 8 weeks after Visit 1
ECG
Time Frame: Up to 8 weeks after Visit 1
Changes in ECGs from baseline.
Up to 8 weeks after Visit 1
Number of Adverse Events, Serious Adverse Events, and Adverse Events of Special Interest
Time Frame: From the time of first dose of osimertinib through 30 days past the last dose of osimertinib or 30 days after Week 72, if osimertinib treatment remains ongoing at Week 72.
To evaluate the safety and tolerability of osimertinib.
From the time of first dose of osimertinib through 30 days past the last dose of osimertinib or 30 days after Week 72, if osimertinib treatment remains ongoing at Week 72.
Physical Exam
Time Frame: From the time of first dose of osimertinib through the date of last dose of osimertinib or at Week 72, whichever comes first.
To evaluate the safety and tolerability of osimertinib.
From the time of first dose of osimertinib through the date of last dose of osimertinib or at Week 72, whichever comes first.
Vital signs
Time Frame: From the time of first dose of osimertinib through the date of last dose of osimertinib or at Week 72, whichever comes first.
To evaluate the safety and tolerability of osimertinib
From the time of first dose of osimertinib through the date of last dose of osimertinib or at Week 72, whichever comes first.
ECG
Time Frame: From the time of first dose of osimertinib through the date of last dose of osimertinib or at Week 72, whichever comes first.
To evaluate the safety and tolerability of osimertinib
From the time of first dose of osimertinib through the date of last dose of osimertinib or at Week 72, whichever comes first.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Collaborators

Medpace, Inc.

Investigators

  • Study Director: Nabil Chehab, PhD, AstraZeneca

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 24, 2017

Primary Completion (Actual)

November 10, 2018

Study Completion (Actual)

November 10, 2018

Study Registration Dates

First Submitted

April 20, 2017

First Submitted That Met QC Criteria

May 1, 2017

First Posted (Actual)

May 2, 2017

Study Record Updates

Last Update Posted (Actual)

November 7, 2019

Last Update Submitted That Met QC Criteria

November 6, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D5160L00032

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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