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A Prospective Study of Plasma Genotyping as a Noninvasive Biomarker for Genotype-directed Cancer Care

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02279004
Recruitment Status : Recruiting
First Posted : October 30, 2014
Last Update Posted : February 6, 2020
Sponsor:
Information provided by (Responsible Party):
Geoffrey Oxnard, MD, Dana-Farber Cancer Institute

Brief Summary:
Tumor genotyping has become an essential biomarker for the care of advanced lung cancer and melanoma, and is currently used to identify patients for treatment with targeted kinase inhibitors like erlotinib and vemurafenib. However, tumor genotyping can be slow and cumbersome, and is limited by availability of tumor biopsy tissue for testing. The aim of this study is to prospectively evaluate a blood-based genotyping tool that can quantify the presence of oncogenic mutations (EGFR, KRAS, BRAF) in patients with lung cancer and melanoma. This assay is being studied both as a diagnostic tool for classifying patient genotype, and a serial measurement tool for quantification of response and progression on therapy.

Condition or disease
NSCLC Melanoma

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Study Type : Observational
Estimated Enrollment : 680 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Prospective Study of Plasma Genotyping as a Noninvasive Biomarker for Genotype-directed Cancer Care
Study Start Date : July 2014
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Melanoma

Group/Cohort
Newly Diagnosed Patients
Newly diagnosed patients with advanced NSCLC or melanoma with complete or planned tissue genotyping.
Acquired Resistance Patients
NSCLC patients with a known EGFR mutation or other targetable mutation and acquired resistance to initial kinase inhibitor therapy.
Known Genotype Patients
NSCLC patients with a known genomic alteration detectable by ddPCR-based plasma genotyping and planned to start a new line of therapy.
Advanced NSCLC
Advanced NSCLC patients with a biopsy planned for tissue genotyping.



Primary Outcome Measures :
  1. Accuracy of Plasma Genotyping Assay [ Time Frame: 2 years ]
    We will determine the accuracy of a droplet digital PCR (ddPCR)-based plasma genotyping assay in performing noninvasive tumor genotyping.


Secondary Outcome Measures :
  1. Turnaround Time of Plasma Genotyping Assay [ Time Frame: 2 years ]
    The amount of time required to perform this noninvasive genotyping assay.

  2. Early Treatment Failure [ Time Frame: 2 years ]
    The ability of serial quantitative ddPCR-based plasma genotyping to predict early treatment failure in patients initiating a new line of therapy.

  3. Accuracy of Plasma NGS [ Time Frame: 2 years ]
    We will determine the accuracy of plasma NGS in performing noninvasive genotyping compared to tumor NGS and paired ddPCR.


Biospecimen Retention:   Samples With DNA
Cell-free plasma DNA (cfDNA) derived from tumor cells


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with NSCLC and advanced melanoma that are either newly diagnosed, have acquired resistance to kinase inhibitor therapy or have a known targetable mutation and are beginning a new line of therapy.
Criteria

Inclusion Criteria

To participate in this study a participant must meet the eligibility of one of the following cohorts:

Cohort 1: Cancers beginning initial treatment

  • One of the following diagnoses:

    • Cohort 1A (CLOSED):

      ---Advanced non-squamous NSCLC (including adenosquamous)

    • Cohort 1B:

      • Stage II-III non-squamous NSCLC (including adenosquamous)
      • Stage IIIB-IV melanoma
  • Patient must be planned to begin initial therapy, or completely resected before or after receiving adjuvant therapy
  • For patients with NSCLC, EGFR and KRAS genotype may be known or unknown
  • For patients with melanoma, BRAF and NRAS genotype may be known or unknown
  • For patients without tumor genotyping, there must be a plan for genotyping including either:

    • Archived tumor tissue available and planned for genotyping
    • A biopsy at some future time is anticipated and will be available for genotyping

Cohort 2: Cancers with acquired resistance to targeted therapy

  • One of the following diagnoses:

    • Cohort 2A (CLOSED):

      ---Advanced NSCLC harboring a known EGFR mutation

    • Cohort 2B:

      • Advanced NSCLC harboring a targetable genotype other than EGFR
      • Advanced melanoma harboring a known tumor genotype
  • Clinical determination of progression targeted therapy, as evidence by plans to start a new systemic treatment regimen, or obtain a biopsy to plan a new treatment regimen

    • New systemic treatment regimen planned OR
    • Re-biopsy for resistance genotyping planned
  • Note, date of targeted therapy start and clinical progression must be provided

Cohort 3: Cancers with a known genotype starting palliative systemic therapy

Cohort 3A (CLOSED):

  • Advanced NSCLC harboring one of the following mutations:

    • EGFR exon 19 deletion
    • EGFR L858R
    • EGFR T790M
    • KRAS G12X
    • BRAF V600E
  • Patients must be initiating palliative systemic therapy, either on or off a clinical trial

Cohort 4: Paired plasma NGS and ddPCR

  • Cohort 4A (CLOSED):

    • Advanced NSCLC, newly diagnosed or with progression following treatment.
    • Biopsy tissue must be available or a biopsy planned and one of the following:

      • Genotyping must have been performed previously
      • Genotyping must be in progress
      • A plan must exist to order genotyping on existing tissue or a planned re-biopsy
    • Patient must not be eligible to enroll in cohort 1A or 2A due to:

      • Not eligible for cohort 1A or 2A
      • Eligible for cohort 1A or 2A but cohort has closed
  • Cohort 4B: Undergenotyped NSCLC

    • Advanced NSCLC, newly diagnosed or with progression following treatment.
    • No known targetable genotype on prior tumor genotyping
    • Biopsy planned for tumor genotyping
  • Cohort 4C: EGFR-mutant NSCLC with acquired resistance

    • Advanced EGFR-mutant NSCLC with progression on EGFR TKI
    • Biopsy planned for resistance genotyping (e.g. T790M, etc)

Exclusion Criteria

  • Participants who are unable to provide informed consent
  • Participants who are 18 years of age or younger
  • Participants who are unable to comply with the study procedures

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02279004


Contacts
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Contact: Yuebi Hu 617-632-4824 yuebi_hu@dfci.harvard.edu
Contact: Ruthia Chen 617-632-6455 ruthia_chen@dfci.harvard.edu

Locations
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United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Yuebi Hu    617-632-4824    yuebi_hu@dfci.harvard.edu   
Contact: Ruthia Hu    617-632-6455    ruthia_chen@dfci.harvard.edu   
Principal Investigator: Geoffrey R Oxnard, M.D.         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
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Principal Investigator: Geoffrey R Oxnard, M.D. Dana-Farber Cancer Institute

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Responsible Party: Geoffrey Oxnard, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT02279004    
Other Study ID Numbers: 14-147
First Posted: October 30, 2014    Key Record Dates
Last Update Posted: February 6, 2020
Last Verified: February 2020
Keywords provided by Geoffrey Oxnard, MD, Dana-Farber Cancer Institute:
Plasma Genotyping
NSCLC
Melanoma
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas