Clinical trial NCT01282658: Pharmacogenomics Study of CPT-11 as the First-line Chemotherapy for mCRC
Official title: Genetic Variants and the Efficacy or Severe Adverse Reactions of CPT-11 Based Regimens in mCRC
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Colorectal Cancer
Keywords: CPT-11,pharmacogenomics,colorectal cancer
Lead sponsor: Huazhong University of Science and Technology
Sponsor class: OTHER
Collaborators: name: Wuhan Union Hospital, China
name: Wuhan University
First posted: 2011-01-25
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: primary care clinic

Brief summary: Irinotecan (CPT-11) is now widely used as the first-line chemotherapy for mCRC. There were 4 key enzymes for CPT-11 metabolizing, CYP3A4, UDP-glucuronosyltransferase, carboxylesterase(CES), and ATP-binding cassette (ABC) transporters. Genetic variations of those enzymes may cause the heterogeneity in safety and efficacy of CPT-11. The aim of this study is to figure out the correlation between the genetic polymorphism and the drug response.

Detailed description: collect blood samples,determining genetic contribution to the safety and efficacy of CPT-11.

Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed colorectal cancer
2. ≥ 18 years old
3. Measurable disease, defined as to RECIST criteria
4. Unresectable metastatic disease OR First recurrence/metastasis after adjuvant therapy and not suitable for operation
5. FOLFIRI±cetuximab/bevacizumab as the first-line therapy
6. Without expected course of radiotherapy during the first-line chemotherapy
7. No previous CPT-11 chemotherapy
8. ECOG performance status (PS) 0-2
9. Not pregnant or nursing and Negative pregnancy test
10. Voluntarily signed the informed consent
11. Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
12. AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN if f liver metastases present)
13. Creatinine clearance \> 50 mL/min OR serum creatinine ≤ 1.5 times ULN

Exclusion Criteria:

1. Brain metastases with obvious symptoms
2. Severe bone marrow failure and can not be corrected
3. Chronic diarrhea history
4. Bowel obstruction without control
5. Mental illness without control
6. Clinically significant (i.e., active) cardiovascular disease, including any of the following: Cerebrovascular accidents/ Myocardial infarction/ Unstable angina/ New York Heart Association class II-IV congestive heart failure/ Serious cardiac arrhythmia requiring medication/ Uncontrolled hypertension
7. Other co-existing malignancy or malignancy diagnosed within the past 5 years, except for basal cell or squamous cell carcinoma, or carcinoma in situ of the cervix
8. Pelvic radiotherapy for the past 1 year
9. Known allergy to any of the components of the study medications
10. Serious, nonhealing wound or ulcer

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Wu han
country: China
facility: Tongji Hospital of Tongji Medical College, Hua Zhong University of Science & Technology
state: Hubei
Study officials:
affiliation: Tongji Hospital of Tongji Medical College, Hua Zhong University of Science & Technology
name: Yuan X Lin, PHD
role: PRINCIPAL_INVESTIGATOR
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