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

NCT03137264 | Completed FDA Drug

• 1 other identifier: D5160L00032
• Study Type: observational
• Target: 44
• Locations: 2 countries
• Sites: 23

Brief Summary

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).

Conditions

Non-small Cell Lung Cancer

Keywords

T790M mutation; EGFR epidermal growth factor receptor; non-invasive testing; lung cancer

Outcome Measures

Primary Outcomes (1)

• The percentage of patients whose T790M results on Trovera urine AND Guardant360 plasma testing match their T790M results on cobas tissue testing.

  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 Outcomes (3)

• 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

Other Outcomes (11)

• Number of procedure-related adverse events and Serious Adverse Events (SAEs)

  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.

  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

  Visit 1 (Day -21 to Day 0)

Study Arms (2)

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

T790M negative

Patients determined to be T790M negative during Part 1 will not be followed for clinical outcomes in Part 2.

Interventions

Other DRUG

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.

Also known as: Standard of Care

T790M positive

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Medpace, Inc.: collaborator

Study Sites (23)

Research Site

Anaheim, California, 92801, United States

Location

Research Site

Los Angeles, California, 90017, United States

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Research Site

Santa Rosa, California, 95403, United States

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Research Site

St. Helena, California, 94574, United States

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Research Site

Deerfield Beach, Florida, 33442, United States

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Research Site

Fort Lauderdale, Florida, 33308, United States

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Research Site

Honolulu, Hawaii, 96819, United States

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Research Site

Boise, Idaho, 83706, United States

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Research Site

Chicago, Illinois, 60612, United States

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Research Site

Harvey, Illinois, 60426, United States

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Research Site

Annapolis, Maryland, 21401, United States

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Research Site

Southfield, Michigan, 48075, United States

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Research Site

Brick, New Jersey, 08724, United States

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Farmington, New Mexico, 87401, United States

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White Plains, New York, 10601, United States

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Asheville, North Carolina, 28801, United States

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Hendersonville, North Carolina, 28792, United States

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Kettering, Ohio, 45409, United States

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Seattle, Washington, 98101, United States

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Seattle, Washington, 98109, United States

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Edmonton, Alberta, T6G 1Z2, Canada

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Newmarket, Ontario, L3Y 2P9, Canada

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Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (11)

• Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008 May;83(5):584-94. doi: 10.4065/83.5.584.

  PMID: 18452692 BACKGROUND

• Morgillo F, Della Corte CM, Fasano M, Ciardiello F. Mechanisms of resistance to EGFR-targeted drugs: lung cancer. ESMO Open. 2016 May 11;1(3):e000060. doi: 10.1136/esmoopen-2016-000060. eCollection 2016.

  PMID: 27843613 BACKGROUND

• Sullivan I, Planchard D. Osimertinib in the treatment of patients with epidermal growth factor receptor T790M mutation-positive metastatic non-small cell lung cancer: clinical trial evidence and experience. Ther Adv Respir Dis. 2016 Dec;10(6):549-565. doi: 10.1177/1753465816670498. Epub 2016 Oct 26.

  PMID: 27784815 BACKGROUND

• Oxnard GR, Thress KS, Alden RS, Lawrance R, Paweletz CP, Cantarini M, Yang JC, Barrett JC, Janne PA. Association Between Plasma Genotyping and Outcomes of Treatment With Osimertinib (AZD9291) in Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2016 Oct 1;34(28):3375-82. doi: 10.1200/JCO.2016.66.7162. Epub 2016 Jun 27.

  PMID: 27354477 BACKGROUND

• Thress KS, Brant R, Carr TH, Dearden S, Jenkins S, Brown H, Hammett T, Cantarini M, Barrett JC. EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of leading technologies to support the clinical development of AZD9291. Lung Cancer. 2015 Dec;90(3):509-15. doi: 10.1016/j.lungcan.2015.10.004. Epub 2015 Oct 9.

  PMID: 26494259 BACKGROUND

• Kawamura T, Kenmotsu H, Taira T, Omori S, Nakashima K, Wakuda K, Ono A, Naito T, Murakami H, Mori K, Nakajima T, Ohde Y, Endo M, Takahashi T. Rebiopsy for patients with non-small-cell lung cancer after epidermal growth factor receptor-tyrosine kinase inhibitor failure. Cancer Sci. 2016 Jul;107(7):1001-5. doi: 10.1111/cas.12963. Epub 2016 Jun 21.

  PMID: 27145431 BACKGROUND

• Lorenz J, Blum M. Complications of percutaneous chest biopsy. Semin Intervent Radiol. 2006 Jun;23(2):188-93. doi: 10.1055/s-2006-941449.

  PMID: 21326762 BACKGROUND

• Reckamp KL, Melnikova VO, Karlovich C, Sequist LV, Camidge DR, Wakelee H, Perol M, Oxnard GR, Kosco K, Croucher P, Samuelsz E, Vibat CR, Guerrero S, Geis J, Berz D, Mann E, Matheny S, Rolfe L, Raponi M, Erlander MG, Gadgeel S. A Highly Sensitive and Quantitative Test Platform for Detection of NSCLC EGFR Mutations in Urine and Plasma. J Thorac Oncol. 2016 Oct;11(10):1690-700. doi: 10.1016/j.jtho.2016.05.035. Epub 2016 Jul 25.

  PMID: 27468937 BACKGROUND

• Shyamala K, Girish HC, Murgod S. Risk of tumor cell seeding through biopsy and aspiration cytology. J Int Soc Prev Community Dent. 2014 Jan;4(1):5-11. doi: 10.4103/2231-0762.129446.

  PMID: 24818087 BACKGROUND

• Goss G, Tsai CM, Shepherd FA, Bazhenova L, Lee JS, Chang GC, Crino L, Satouchi M, Chu Q, Hida T, Han JY, Juan O, Dunphy F, Nishio M, Kang JH, Majem M, Mann H, Cantarini M, Ghiorghiu S, Mitsudomi T. Osimertinib for pretreated EGFR Thr790Met-positive advanced non-small-cell lung cancer (AURA2): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1643-1652. doi: 10.1016/S1470-2045(16)30508-3. Epub 2016 Oct 14.

  PMID: 27751847 BACKGROUND

• Soria JC, Wu YL, Nakagawa K, Kim SW, Yang JJ, Ahn MJ, Wang J, Yang JC, Lu Y, Atagi S, Ponce S, Lee DH, Liu Y, Yoh K, Zhou JY, Shi X, Webster A, Jiang H, Mok TS. Gefitinib plus chemotherapy versus placebo plus chemotherapy in EGFR-mutation-positive non-small-cell lung cancer after progression on first-line gefitinib (IMPRESS): a phase 3 randomised trial. Lancet Oncol. 2015 Aug;16(8):990-8. doi: 10.1016/S1470-2045(15)00121-7. Epub 2015 Jul 6.

  PMID: 26159065 BACKGROUND

Related Links

• Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 \[Internet\]. Lyon, France: International Agency for Research on Cancer; 2013. Accessed on 18 January 2017.
• Related Info
• redacted synopsis

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, urine, and tissue

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Nabil Chehab, PhD

  AstraZeneca

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: May 2, 2017
• Study Start: October 24, 2017
• Primary Completion: November 10, 2018
• Study Completion: November 10, 2018
• Last Updated: November 7, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (20); CA (3)