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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Observational
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion 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) Cohort 5: Genotyped KRAS patients starting palliative systemic therapy.
  • - Advanced NSCLC harboring a KRAS exon 2 mutation.
  • - Patients must be initiating new systemic therapy, either on or off a clinical trial.
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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT02279004
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Dana-Farber Cancer Institute
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Julia Rotow, M.D.
Principal Investigator Affiliation Dana-Farber Cancer Institute
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

NSCLC, Melanoma
Arms & Interventions

Arms

: 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.

Interventions

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Dana-Farber Cancer Institute, Boston, Massachusetts

Status

Recruiting

Address

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Site Contact

Andy Pangilinan

[email protected]

617-632-4824

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