An Exploratory Study of Chemotherapy for Metastatic Colorectal Cancer Based Upon Thymidine Phosphorylase Expression, KRAS and BRAF Mutation Status, and ERCC1 Expression
I. To evaluate the feasibility, as defined by completion of three specific marker assays and
generation of clinically meaningful endpoints, of selecting treatment regimen components
based on biologic tumor characteristics in chemotherapy-naïve patients with metastatic
I. To investigate the response rate associated with genotype/phenotype guided therapy using
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
II. To investigate the time to failure of treatment strategy associated with
genotype/phenotype guided therapy, defined as the time from initiation of investigational
treatment strategy until death, disease progression, initiation of a new therapeutic agent,
or disease progression while on a partial or complete treatment holiday.
III. To investigate the progression-free survival associated with genotype/phenotype guided
therapy, defined as the time from enrollment to time of progression of disease or death.
OUTLINE: Patients are assigned to treatment groups based on marker assay results.
ARM A: TP-/uncertain, KRAS and BRAF wild-type, ERCC1 high ARM B: TP-/uncertain, KRAS and
BRAF wild-type, ERCC1 low/uncertain ARM C: TP-/uncertain, KRAS or BRAF mutant/uncertain,
ERCC1 high ARM D: TP-/uncertain, KRAS or BRAF mutant/uncertain, ERCC1 low/uncertain ARM E:
TP+, KRAS and BRAF wild-type, ERCC1 high ARM F: TP+, KRAS and BRAF wild-type, ERCC1
low/uncertain ARM G: TP+, KRAS or BRAF mutant/uncertain, ERCC1 high ARM H: TP+, KRAS or BRAF
mutant/uncertain, ERCC1 low/uncertain ARM I: TP uninterpretable, KRAS or BRAF
uninterpretable, ERCC1 uninterpretable
KRAS testing is standard of care in patients with metastatic colorectal cancer; tymidine
phosphorylase, ERCC1 and BRAF testing assays are still experimental.
Courses in arms A-D and arm I repeat every 28 days and courses in arms E-H repeat every 21
days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 18 months.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Feasibility, defined as a sufficient proportion of subjects having available tissue and an acceptable composite assay success rate among tested subjects
Over 21 months
Fox Chase Cancer Center
United States: Federal Government
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