Official Title
The Identification, Validation and Implementation of Molecular Markers to Predict Response to Fluorouracil-based Adjuvant Chemotherapy in Stage III Colorectal Cancer Patients - Prospective Clinical Observational Study
Brief Title
Genetic and Epigenetic Determinants of Response to Fluorouracil-based Adjuvant Chemotherapy in Patients With Stage III Colorectal Cancer
Protocol ID
NCT03127111
Lead Sponsor
Renmin Hospital of Wuhan University
Brief Summary
The goal of this laboratory research is to look for genetic and epigenetic markers that
can predict which patients with stage III colorectal cancer will benefit from
fluorouracil-based adjuvant chemotherapy.
Detailed Description
This is a prospective project in collecting and assessing clinical outcomes data related
to molecular profiling of tumors based on samples from peripheral blood, primary tumor,
and adjacent normal colorectal tissue.
Objectives:
1. Validation of predictive value of known markers CpG island methylator phenotype
(CIMP) and microsatellite instability (MSI) in the response to 5-fluorouracil-based
chemotherapy in patients with stage III colorectal cancer.
2. Exploratory evaluation of the potential predictive values of known genetic
variations including, but not limited to, KRAS mutations, BRAF mutations, PIK3A
mutations, and EGFR mutations, etc.
3. Exploratory identification and evaluation of the predictive value of novel
methylation aberrations identified by whole-genome bisulfite sequencing.
4. Exploratory identification and evaluation of the predictive value of novel genetic
aberrations discovered by RNA-sequencing (RNA-seq) or genome-wide association study
(GWAS).
Outline:
Blood is collected at baseline and examined for single-nucleotide polymorphisms (SNPs)
and expression level of specific gene. Tumor and corresponding normal tissue at surgical
resection and assessed for gene methylations, mutations, and expressions.
Study Period
-
Enrollment Count
300 participants
Eligibility Criteria
Inclusion Criteria:
1. Requirements for tumor parameters
1. Histologically confirmed colorectal adenocarcinoma.
2. Stage III disease (any pT, N1-2, M0).
3. Tumors must have been curatively resected (R0).
4. No evidence of residual involved lymph node disease or metastatic disease at
the time of registration.
2. Requirements for patient characteristics
1. Patient is ≥ 18 years of age on the day of consenting to the study.
2. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1 at the
time of screening.
3. Fertile patients must use effective contraception.
4. Patients must demonstrate ability to understand and the willingness to sign a
written informed consent document.
5. Patients must demonstrate ability to complete study questionnaires.
6. Patients must provide written informed consent prior to performance of
study-specific procedures or assessments and must be willing to comply with
treatment and follow up.
3. Required initial laboratory values
1. Leukocytes ≥ 3,000/mm^3
2. Absolute neutrophil count ≥ 1,500/mm^3
3. Platelet count ≥ 100,000/mm^3
4. Creatinine ≤ 1.5 times upper limit of normal (ULN)
5. Total Bilirubin ≤ 1.5 times ULN
6. Aspartate aminotransferase (AST) ≤ 2.5 times ULN
7. Alanine aminotransferase (ALT) ≤ 2.5 times ULN
Exclusion Criteria:
1. Patients with a known history of allergic reactions attributed to compounds of
similar chemical or biologic composition to fluorouracil.
2. Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection-requiring intravenous antibiotics, or psychological, familial,
sociological, or geographical condition that would limit compliance with study
requirements
3. Following cardiovascular conditions within the past 6 months: Myocardial infarction,
unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac
arrhythmia, cerebrovascular accident or transient ischemic attack, deep vein
thrombosis, other significant thromboembolic event.
4. Known human immunodeficiency virus (HIV)-positive patients and those with known
hepatitis B or C.
5. Patients with evidence of other primary malignancies within the past 5 years,
excluding adequately treated basal cell carcinoma of the skin or carcinoma in situ
of the cervix.
6. Pregnant or nursing.
Filters
Stage III Colorectal Cancer
NOT_YET_RECRUITING
ADULT
OLDER_ADULT