Pharmacogenomics Study of CPT-11 as the First-line Chemotherapy for mCRC

Colorectal Cancer Clinical Trial

— PSIFL  

Official title:

Genetic Variants and the Efficacy or Severe Adverse Reactions of CPT-11 Based Regimens in mCRC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01282658
• Other study ID #: TJCC-001
• Status: Recruiting
• Phase: N/A
• First received: January 24, 2011
• Last updated: February 16, 2011
• Start date: November 2010
• Est. completion date: May 2013

Study information

• Verified date: November 2010
• Source: Huazhong University of Science and Technology
• Contact: Yuan X Lin, PHD
• Phone: 0086-02783663342
• Email: yxl[@]medmail.com.cn
• Is FDA regulated: No
• Health authority: China: Ethics Committee
• Study type: Observational

Clinical Trial 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.

Description:

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Locations

Country	Name	City	State
China	Tongji Hospital of Tongji Medical College, Hua Zhong University of Science & Technology	Wu han	Hubei

Sponsors (3)

Lead Sponsor	Collaborator
Huazhong University of Science and Technology	Wuhan Union Hospital, China, Wuhan University

Country where clinical trial is conducted

China, 

References & Publications (16)

A Report of Cancer Incidence and Mortality from 34 Cancer Registries in China,2006. China Cancer 19:356-65, 2010

Ando Y, Hasegawa Y. Clinical pharmacogenetics of irinotecan (CPT-11). Drug Metab Rev. 2005;37(3):565-74. Review. — View Citation

Braun MS, Richman SD, Quirke P, Daly C, Adlard JW, Elliott F, Barrett JH, Selby P, Meade AM, Stephens RJ, Parmar MK, Seymour MT. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol. 2008 Jun 1;26(16):2690-8. doi: 10.1200/JCO.2007.15.5580. Erratum in: J Clin Oncol. 2008 Sep 10;26(26):4363. — View Citation

Carlini LE, Meropol NJ, Bever J, Andria ML, Hill T, Gold P, Rogatko A, Wang H, Blanchard RL. UGT1A7 and UGT1A9 polymorphisms predict response and toxicity in colorectal cancer patients treated with capecitabine/irinotecan. Clin Cancer Res. 2005 Feb 1;11(3):1226-36. — View Citation

Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000 Mar 25;355(9209):1041-7. Erratum in: Lancet 2000 Apr 15;355(9212):1372. — View Citation

Hoskins JM, Marcuello E, Altes A, Marsh S, Maxwell T, Van Booven DJ, Paré L, Culverhouse R, McLeod HL, Baiget M. Irinotecan pharmacogenetics: influence of pharmacodynamic genes. Clin Cancer Res. 2008 Mar 15;14(6):1788-96. doi: 10.1158/1078-0432.CCR-07-1472. — View Citation

Innocenti F, Undevia SD, Iyer L, Chen PX, Das S, Kocherginsky M, Karrison T, Janisch L, Ramírez J, Rudin CM, Vokes EE, Ratain MJ. Genetic variants in the UDP-glucuronosyltransferase 1A1 gene predict the risk of severe neutropenia of irinotecan. J Clin Oncol. 2004 Apr 15;22(8):1382-8. Epub 2004 Mar 8. — View Citation

Marcuello E, Altés A, Menoyo A, Del Rio E, Gómez-Pardo M, Baiget M. UGT1A1 gene variations and irinotecan treatment in patients with metastatic colorectal cancer. Br J Cancer. 2004 Aug 16;91(4):678-82. — View Citation

Mathijssen RH, Marsh S, Karlsson MO, Xie R, Baker SD, Verweij J, Sparreboom A, McLeod HL. Irinotecan pathway genotype analysis to predict pharmacokinetics. Clin Cancer Res. 2003 Aug 15;9(9):3246-53. — View Citation

Paradiso A, Xu J, Mangia A, Chiriatti A, Simone G, Zito A, Montemurro S, Giuliani F, Maiello E, Colucci G. Topoisomerase-I, thymidylate synthase primary tumour expression and clinical efficacy of 5-FU/CPT-11 chemotherapy in advanced colorectal cancer patients. Int J Cancer. 2004 Aug 20;111(2):252-8. — View Citation

Ramchandani RP, Wang Y, Booth BP, Ibrahim A, Johnson JR, Rahman A, Mehta M, Innocenti F, Ratain MJ, Gobburu JV. The role of SN-38 exposure, UGT1A1*28 polymorphism, and baseline bilirubin level in predicting severe irinotecan toxicity. J Clin Pharmacol. 2007 Jan;47(1):78-86. — View Citation

Rhodes KE, Zhang W, Yang D, Press OA, Gordon M, Vallböhmer D, Schultheis AM, Lurje G, Ladner RD, Fazzone W, Iqbal S, Lenz HJ. ABCB1, SLCO1B1 and UGT1A1 gene polymorphisms are associated with toxicity in metastatic colorectal cancer patients treated with first-line irinotecan. Drug Metab Lett. 2007 Jan;1(1):23-30. — View Citation

Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000 Sep 28;343(13):905-14. — View Citation

Smith NF, Figg WD, Sparreboom A. Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro. 2006 Mar;20(2):163-75. Epub 2005 Nov 3. Review. — View Citation

Van Cutsem E, Nordlinger B, Adam R, Köhne CH, Pozzo C, Poston G, Ychou M, Rougier P; European Colorectal Metastases Treatment Group. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006 Sep;42(14):2212-21. Epub 2006 Aug 10. Review. — View Citation

Yoo PS, Lopez-Soler RI, Longo WE, Cha CH. Liver resection for metastatic colorectal cancer in the age of neoadjuvant chemotherapy and bevacizumab. Clin Colorectal Cancer. 2006 Sep;6(3):202-7. Review. — View Citation

* Note: There are 16 references in all — Click here to view all references