Patient case: 68-year-old male with colon cancer; genetic feature: MLH1 methylation suppression (microsatellite instability)

Clinical trial: Genetic Testing in Screening Patients With Metastatic or Unresectable Colon or Rectal Cancer For a COLOMATE Trial

Summary: This trial screens patients with colon or rectal cancer that has spread to other places in the body or cannot be removed by surgery for genetic mutations for recommendation to a molecularly assigned therapy. Identifying gene mutations may help patients enroll onto target companion trials that target these mutations.

Detailed description: PRIMARY OBJECTIVES:
  I. To perform blood-based genomic profiling on patients with treatment refractory metastatic colorectal cancer (CRC) to facilitate accrual to molecularly assigned therapies.
  II. To obtain tumor tissue and patient-matched tumor deoxyribonucleic acid (DNA) from peripheral blood to facilitate clinically annotated genomic analyses.
  CORRELATIVE RESEARCH OBJECTIVES:
  I. To explore mechanisms of acquired resistance to molecularly assigned therapy.
  II. To explore the correlation between circulating cell free tumor DNA (cfDNA) mutational burden (allele frequency, copy number) and clinical outcomes (overall response rate [ORR], progression free survival [PFS], overall survival [OS]).
  OUTLINE:
  Patients submit blood samples for genetic testing.

Eligibility: Inclusion Criteria:
  -  Histological confirmation of adenocarcinoma of the colon or rectum that is metastatic and/ or unresectable
  -  Progression, intolerance, or contraindication to a fluoropyrimidine (e.g., 5- fluorouracil or capecitabine), oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ziv-aflibercept, or ramucirumab), and an anti-PD-1 monoclonal antibody (nivolumab or pembrolizumab) if tumor has deficient mismatch repair proteins (dMMR) or is microsatellite instability-high (MSI-H)
  -  For patients with KRAS and NRAS wild-type tumors, progression, intolerance, or contraindication to an anti-EGFR monoclonal antibody (cetuximab or panitumumab)
  -  Note: If tissue is known to be positive for HER2 expression (IHC 3+) or the tumor has ERBB2 (HER2) amplification detected by a Clinical Laboratory Improvement Act (CLIA)-certified assay, prior treatment with anti-EGFR therapy is not required
  -  At least one site of disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.1) that has not been previously irradiated; if the patient has had previous radiation to the target lesion(s), there must be evidence of progression since the radiation
  -  Life expectancy >= 3 months per estimation of investigator
  -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  -  Capable of understanding and complying with the protocol requirements and has signed the informed consent document
  Exclusion Criteria:
  -  Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator would interfere with conduct of the study or study results
  -  Evidence within the last 3 years of another malignancy which required systemic treatment. EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
  -  Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

Relevance to patient case: not relevant