Treatment Outcomes of Hepatic Metastasis After FOLFOX-4 Therapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2012 by National Taiwan University Hospital
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00610636
First received: January 28, 2008
Last updated: December 6, 2012
Last verified: December 2012
  Purpose

The role of surgical resection in the subset of patients with resectable hepatic metastases converted from initially non-resectable liver metastasis was still not clearly established. To further explore the oncologic results of surgical versus non-surgical methods for the treatment of this subset of patients, we designed and conducted the present randomized prospective study beginning in 2002. The present study was based on the following arguments against the predominant survival benefits of surgical resection in previous reported series: (1) The initially non-resectable liver metastasis was basically a disseminated disease, even though some metastases were highly responsive to chemotherapy and become resectable; (2) Since the evaluation of resectability was based on the imaging studies, it was difficult to consider the surgical resection as "curative" for the resectable hepatic metastases converted from non-resectable ones, given the limitation of the current imaging stools of high-technology; (3) The resectable hepatic metastases after neoadjuvant chemotherapy might represent a subset of hepatic metastases biologically highly responsive to chemotherapy and the time-to-progression for these metastases might be fairly long after a response. Additionally, these metastases might be also biologically responsive to other cytotoxic or targeted therapies that justified the patients' continuous adoption of non-surgical treatment.


Condition Intervention Phase
Colorectal Cancer
Procedure: Hepatic resection
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Oncologic Outcomes of Surgical Versus Non-surgical Methods for the Treatment of Resectable Colorectal Liver-confined Metastases Converted From Initially Non-resectable Metastases by FOLFOX-4 Neoadjuvant Chemotherapy: A Randomized Clinical Trial

Resource links provided by NLM:


Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • Both groups of patients were analyzed with intention-to-treat principle. The primary end-point was time-to-progression. The secondary points were overall survival and surgical morbidity. [ Time Frame: evaluated every 6 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Surgical morbidity, Chemotherapeutic complications [ Time Frame: Evaluated every 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 200
Study Start Date: January 2002
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
The patients with secondary resectable colorectal hepatic metastasis undergoing surgery
Procedure: Hepatic resection
Hepatic resection
Active Comparator: 2
The patients with secondary resectable colorectal hepatic metastasis who underwent continuous chemotherapy
Procedure: Hepatic resection
Hepatic resection

Detailed Description:

In 2000, de Gramont et al. and Giacchetti et al. reported that combination chemotherapy including modulated infusional 5-Fu plus irinotecan and oxaliplatin could achieve a response rate of approximately 50% and a median survival of in excess of 20 months. These encouraging results implied that chemotherapy is likely to play an increasingly important role in decreasing the size of metastasis to allow for liver resection. Interestingly, Adam and Bismuth et al. reported that the 5-year overall survival of 50% (95% confidence interval 33-68%), observed in patients with resection following neoadjuvant chemotherapy, was comparable to patients with primarily resectable hepatic metastasis as reported by Scheele et al. (39%, 469 patients), Fong et al. (37%, 1001 patients), Nordlinger et al.(28%, 1568 patients), and Fiqueras et al. (36%, 235 patients). Recently, Zelek et al. reported that intravenous and hepatic artery infusion of irinotecan/ 5-fluorouracil/ leucovorin could facilitate complete resection of initially non-resectable hepatic metastases. Pozzo et al. indicated that neoadjuvant treatment of unresectable liver disease with irinotecan/ 5-fluorouracil/ leucovorin enabled a significant portion of patients to undergo surgical resection. Alberts et al. showed that FOLFOX-4 therapy allowed for successful resection of disease in a portion of patients initially not judged to be optimally resectable but with a high recurrence rate after surgery. Masi et al. reported that neoadjuvant approach with irinotecan plus FOLFOX-4 had significant antitumor activity and provided a radical surgical resection of initially unresctable hepatic colorectal metastases with promising median survival of patients. However, most studies published till now are retrospective analyses without a control group or case series with limited patient number and/or short time of follow-up. Therefore, the role of surgical resection in the subset of patients with resectable hepatic metastases converted from initially non-resectable liver metastasis was still not clearly established. To further explore the oncologic results of surgical versus non-surgical methods for the treatment of this subset of patients, we designed and conducted the present randomized prospective study beginning in 2002. The present study was based on the following arguments against the predominant survival benefits of surgical resection in previous reported series: (1) The initially non-resectable liver metastasis was basically a disseminated disease, even though some metastases were highly responsive to chemotherapy and become resectable; (2) Since the evaluation of resectability was based on the imaging studies, it was difficult to consider the surgical resection as "curative" for the resectable hepatic metastases converted from non-resectable ones, given the limitation of the current imaging stools of high-technology; (3) The resectable hepatic metastases after neoadjuvant chemotherapy might represent a subset of hepatic metastases biologically highly responsive to chemotherapy and the time-to-progression for these metastases might be fairly long after a response. Additionally, these metastases might be also biologically responsive to other cytotoxic or targeted therapies that justified the patients' continuous adoption of non-surgical treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Secondary resectable hepatic metastasis converted by FOLFOX-4 regimen.
  2. age between 18-80 y/o.
  3. no extra-hepatic disease
  4. life expectancy ≥ 3 months
  5. Karnofsky performance status ≥ 50%.
  6. WBC count ≥ 4,000/μl, platelet count ≥ 100,000/μl, serum bilirubin ≤ 2.0 mg/dl and normal serum glucose and electrolyte levels.-

Exclusion Criteria:

  1. Secondary resectable hepatic metastasis with extra-hepatic disease
  2. poor liver function including: serum bilirubin > 2.0 mg/dl, GOT,GPT >100 U/L
  3. severe steatosis hepatitis or sinusoidal dilation
  4. Karnoofsky performance status <50%.-
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00610636

Contacts
Contact: Jin-Tung Liang, PhD 886-2-23123456 ext 5683 jintung@ntu.edu.tw

Locations
Taiwan
Division of Colorectal Surgery, Department of Surgery , National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Jin-Tung Liang, PhD    886-2-23123456 ext 5683    jintung@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Principal Investigator: Jin-Tung Liang, PhD National Taiwan University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00610636     History of Changes
Other Study ID Numbers: 9100015204, NSC94-2314-B002-288
Study First Received: January 28, 2008
Last Updated: December 6, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
FOLFOX-4
neoadjuvant chemotherapy
colorectal cancer
liver metastasis
resectability

Additional relevant MeSH terms:
Colorectal Neoplasms
Neoplasm Metastasis
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplastic Processes
Pathologic Processes

ClinicalTrials.gov processed this record on October 19, 2014