Pre- and Post-Operative FOLFOX Based Therapy for Patients With Colorectal Cancer With Liver Involvement - Tabular View

This Tabular View shows the required WHO registration data elements as marked by ^†

Tracking Information

First Received Date ^†

September 27, 2007

Last Updated Date

February 17, 2009

Start Date ^†

June 2007

Current Primary Outcome Measures ^†

Total postoperative complication rate (Fraction of patients with any grade of complication I-V) at 30 days [ Time Frame: 30 days following surgery ] [ Designated as safety issue: Yes ]
Major postoperative complication rate (Fraction of patients with any complication grades IV and V) at 30 days [ Time Frame: 30 days following surgery ] [ Designated as safety issue: Yes ]
All-cause mortality at 30 days postoperatively [ Time Frame: 30 days following surgery ] [ Designated as safety issue: Yes ]

Original Primary Outcome Measures ^†

Same as current

Change History

Complete list of historical versions of study NCT00537823 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^†

Study postoperative recurrence patters (liver only vs distant disease) [ Time Frame: 1, 3, 5 years ] [ Designated as safety issue: No ]
Calculate liver recurrence-free survival at one, three, and five years [ Time Frame: 1, 3, 5 years ] [ Designated as safety issue: No ]
Document the histologic hepatic toxicity at operation [ Time Frame: Time of operation ] [ Designated as safety issue: Yes ]
Provide the nonalcoholic steatohepatitis score (0-3) [ Time Frame: Time of operation. ] [ Designated as safety issue: No ]
Provide the liver injury scale score (0-27) [ Time Frame: Time of surgery. ] [ Designated as safety issue: Yes ]
Describe the effect of preoperative chemotherapy on tumor size [ Time Frame: Upon completion of neoadjuvant chemotherapy. ] [ Designated as safety issue: No ]
Calculate change in tumor size from pretreatment to preoperative CT scan [ Time Frame: Approximately 2 months. ] [ Designated as safety issue: No ]

Original Secondary Outcome Measures ^†

Same as current

Descriptive Information

Brief Title ^†

Pre- and Post-Operative FOLFOX Based Therapy for Patients With Colorectal Cancer With Liver Involvement

Official Title ^†

Effect of Short-Duration Preoperative Neoadjuvant Therapy With a Combination of FOLFOX Based Therapy on Morbidity After Liver Resection for Colorectal Cancer Metastases

Brief Summary

The purpose of this study is to determine the effect of short-duration pre-operative FOLFOX based therapy on postoperative problems after liver surgery for patients with metastatic colorectal cancer.

Detailed Description

Although early stage, localized colon and rectal cancers are associated with 5 year survival rates of nearly 90%, only a minority of patients present with localized disease. Unfortunately, at the time of their initial presentation, approximately 35% of patients with colon or rectal cancer have metastatic disease. Nearly two thirds of these patients with stage IV disease have evidence of extrahepatic spread and have a median overall survival rate of 8-10 months in the absence of further treatment. Even with the most intensive chemotherapeutic regimens, the median overall survival for these patients ranges from 12 months to 20 months. However, a small subset of patients with stage IV disease has isolated hepatic metastatic disease and can undergo resection. The patients with completely resected liver metastases enjoy a significantly higher overall five-year survival, which is as high as 58% in carefully selected patients. Ten-year overall survival has been reported in 22% of patients. Despite this improvement, the five-year disease-free survival for these patients is at best 35%, with hepatic recurrences occurring in 46%.

The fact that adjuvant chemotherapy improves the three-year survival rate for stage II disease and five-year survival rates for stage III disease implies that it can treat micrometastatic disease in some fraction of patients. Because micrometastatic disease is likely the cause of the high recurrence rate in patients who undergo liver resection, there is a clear biologic rationale for using postoperative adjuvant chemotherapy after liver resection.

Although this strategy is a common practice in many centers, no convincing data that this improves survival have been reported. A large randomized phase III trial (EORTC 40983) examining this question is currently ongoing and effect on survival has not yet been reported. Given that systemic chemotherapy after liver resection remains of unproven benefit at the present time, many have wondered if preoperative treatment might have more promise in improving recurrence rates.

Study Phase

Phase II

Study Type ^†

Interventional

Study Design ^†

Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study

Condition ^†

Colorectal Cancer
Metastases

Intervention ^†

Drug: FOLFOX 6
Drug: Cetuximab
Drug: Bevacizumab

Study Arms / Comparison Groups

Experimental: FOLFOX + C225 (for patients who have Wildtype after K-Ras testing) OR FOLFOX + Bevacizumab (for patients who have K-Ras 12/13 codon mutation after K-Ras testing)

Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status ^†

Recruiting

Enrollment ^†

Estimated Completion Date

June 2009

Estimated Primary Completion Date

October 2008 (final data collection date for primary outcome measure)

Eligibility Criteria ^†

Inclusion Criteria:

Synchronous or metachronous colorectal metastases
Technically resectable liver metastases
Four or fewer metastases
No tumors in porta hepatis
Resection of no more than 70% of liver needed
Medically suitable candidate for major liver resection
FDG-PET scan without metastatic disease outside the liver

Exclusion Criteria:

Near-obstructing or obstructing colon lesions in patients in whom combined resection is planned (as delay for preoperative chemotherapy would be medially impossible)
Treatment with FOLFOX or cetuximab within 12 months
Treatment with irinotecan within 12 months
Abnormal liver function (ALT or AST > 5x ULN, bilirubin > 3x ULN)
Body mass index >/= 35 kg/m² (as the risk for steatohepatitis is increased)
Renal insufficiency (Cr > 2.5mg/dL)
Interstitial lung disease (because cetuximab has been rarely associated with development of interstitial lung disease)
ECOG performance score >/= 3
Patients unable to give informed consent
Pregnant patient (as cetuximab is a Class C drug)
Peripheral neuropathy >/= grade II (as oxaliplatin causes neuropathy to worsen)

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^††

Contact: David Linehan, MD	314-747-2938	linehand@wustl.edu
Contact: Farley Johnson	314-747-9202	johnsonf@ccadmin.wustl.edu

Location Countries ^†

United States

Expanded Access Status

Administrative Information

NCT ID ^†

NCT00537823

Responsible Party

David Linehan, MD, Washington University School of Medicine

Secondary IDs ^††

Study Sponsor ^†

Washington University School of Medicine

Collaborators ^††

Investigators ^†

Principal Investigator:

David Linehan, MD

Washington University School of Medicine

Information Provided By

Washington University School of Medicine

Verification Date

February 2009

^† Required WHO trial registration data element.
^†† WHO trial registration data element that is required only if it exists.