Phase 3 Study of Surgery Combined With Neoadjuvant Chemotherapy(XELOX) in Colorectal Cancer With Resectable Liver Metastasis

A Phase III Study of Surgery in Combination With Neoadjuvant Chemotherapy of Oxaliplatin Plus Capecitabine in Colorectal Cancer With Respectable Liver Metastasis

This study aims to discuss the efficacy and safety of neoadjuvant chemotherapy with XELOX regimen (oxaliplatin plus capecitabine) .

Study Overview

• Status: Unknown
• Conditions: Colorectal Cancer; Resectable Liver Metastasis
• Intervention / Treatment: Drug: neoadjuvant chemotherapy with oxaliplatin and capecitabine; Procedure: resection of liver metastasis

Detailed Description

Liver metastasis is the most important prognostic factor of colorectal cancer. Reasonable multidisciplinary therapy might improve the prognosis of patients with liver metastasis. Surgery has been the first choice under such situation. Recently, neoadjuvant chemotherapy has also shown its value in unresectable liver metastasis, for it can increase the chance of R0 resection and give some clues to chemosensitivity of agents. However, for those resectable lesions, the role and safety of neoadjuvant chemotherapy has yet to be confirmed. so we design this study.

• Study Type: Interventional
• Enrollment (Anticipated): 392
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: zhou jing, MD; Phone Number: 86-10-66583821; Email: zhoujing58@sohu.com
• Study Contact Backup: Name: Xiaotian Zhang, MD; Phone Number: 86-10-88196561; Email: zhangxt@yahoo.com

Study Locations

• China
  • Beijing, China, 100044
    • Recruiting
    • Peking University, People's Hospital
    • Contact: jing zhou, MD; Phone Number: 86-10-66583821; Email: zhoujing58@sohu.com
  • Beijing
    • Beijing, Beijing, China, 100036
      • Recruiting
      • Peking University, School of Oncology
      • Contact: Xiaotian Zhang, MD; Phone Number: 86-10-88196561; Email: zhangxt@yahoo.com
      • Contact: jifang gong, MD; Phone Number: 86-10-88196088; Email: goodjf@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Histologically confirmed colorectal cancer with liver metastasis(all patients should have the pathological report of colorectal cancer. The chances of hepatocellular carcinoma or metastasis from other primary lesions should be excluded. )
2. Liver metastasis should be resected with R0 resection and to save enough normal liver tissue
3. Anticipated liver resection: for normal liver, ﹤70%; for liver with cirrhosis, ﹤50%
4. No metastasis of other organs or lymph nodes in abdominal cavity
5. No previous use of oxaliplatin and capecitabine, or previous adjuvant treatment ended more than 6 months
6. Age 18 to 75 years old
7. Karnofsky performance status ≥70
8. Life expectancy of ≥3 month
9. Bilirubin level < 1.5mg/dL
10. Serum creatinine <1.0 times ULN
11. Absolute neutrophil count ≥2000/mm3, platelet>100,000/mm3, Hb>9g/dl
12. Having signed informed consent

Exclusion Criteria:

1. previous use of oxaliplatin or fluorouracil-based chemotherapy in 6 months.
2. No R0 resection or not enough normal liver tissue left
3. previous radiotherapy of target lesions
4. accompanied with unresectable other metastasis or malignant pleural fluids or ascites.
5. complete or uncompleted liver obstruction
6. peripheral neuropathy(NCI-CTC grade 1 or more)
7. mental disturbance neuropathy that influence the cognition, including brain metastasis
8. other serious disease such as uncontrollable active infection, heart infarction with 1 year, un controlled hypertension, arrhythmia with high risk, or unstable heart infarction,heart failure, coronary artery disease, myocardial infarction within the last 6 months
9. Other previous malignancy within 5 year, except non-melanoma skin cancer
10. accompany with other anti-tumor therapies,including immune therapy, intervention or injection with chemotherapeutical agents into serous cavity, or participating other clinical trials.
11. Pregnancy or lactation period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 2~3 cycles of neoadjuvant chemotherapy before resection of liver metastasis	Drug: neoadjuvant chemotherapy with oxaliplatin and capecitabine; oxaliplatin: 130mg/m2, d1(Q3w) capecitabine:1000mg/m2 bid, d1-14(Q3w); Procedure: resection of liver metastasis; surgery with the aim of R0 resection
Active Comparator: 2; no neoadjuvant chemotherapy, resect the liver metastasis directly	Procedure: resection of liver metastasis; surgery with the aim of R0 resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
disease free survival rate	3 year

Secondary Outcome Measures

Outcome Measure	Time Frame
R0 resection rate	at the time of pathological report
survival rate and over survival	5 year
surgery related mortality	peri-operation period
response rate and safety of XELOX as a neoadjuvant regimen	no time frame

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Collaborators: Peking University; Sanofi
• Investigators: Principal Investigator: Lin Shen, MD, Peking University, School of Oncology, Department of GI oncology; Principal Investigator: Shan Wang, MD, Peking University People's Hospital, Department of General Surgery

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Anticipated): June 1, 2010
• Study Completion (Anticipated): June 1, 2015

Study Registration Dates

• First Submitted: February 26, 2008
• First Submitted That Met QC Criteria: March 5, 2008
• First Posted (Estimate): March 6, 2008

Study Record Updates

• Last Update Posted (Estimate): March 6, 2008
• Last Update Submitted That Met QC Criteria: March 5, 2008
• Last Verified: February 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Liver Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis; Liver Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine; Oxaliplatin
• Other Study ID Numbers: OXALIC