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

Dana-Farber Cancer Institute

Status

Enrolling

Conditions

Melanoma

NSCLC

Study type

Observational

Funder types

Other

Identifiers

NCT02279004

14-147

Details and patient eligibility

About

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.

Enrollment

840 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and 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)