Liver Resection and Floxuridine Plus Fluorouracil and Leucovorin in Treating Patients With Liver Metastases From Colorectal Cancer

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

floxuridine

fluorouracil

leucovorin calcium

adjuvant therapy

conventional surgery

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, liver metastases

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Histologically confirmed colorectal carcinoma or radiologically confirmed colorectal carcinoma in a synchronous metastasis Intrahepatic metastases required No more than 15 metastases involving no more than 60% of functioning liver No extrahepatic disease unless: Resectable anastomotic or locally recurrent tumor Resectable mesenteric lymph node involvement in patients undergoing initial resection of primary colorectal carcinoma Disease extension from liver metastasis amenable to en bloc resection (e.g., diaphragm wall, kidney, abdominal wall) No biopsy-proven chronic active hepatitis PATIENT CHARACTERISTICS: Age: Physiologic 18 to 70 Performance status: Karnofsky 60%-100% Hematopoietic: AGC at least 1,500 Platelets at least 100,000 Hepatic: Bilirubin no greater than 2.0 mg/dL (unless reversibly obstructed by metastasis) Renal: Creatinine no greater than 2.0 mg/dL Other: No second malignancy within 5 years except adequately treated: Nonmelanomatous skin cancer In situ bladder cancer In situ cervical cancer No pregnant women PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior mitomycin or nitrosoureas allowed Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the liver At least 3 weeks since radiotherapy and recovered Prior pelvic radiotherapy allowed No planned concurrent radiotherapy Surgery: Not specified

Sites / Locations

City of Hope Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin

Arm Description

Patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks

Outcomes

Primary Outcome Measures

2 Year Disease-free Survival .

Estimated using the product-limit method of Kaplan and Meier. Disease free survival, defined as first documented evidence of treatment failure. Acceptable evidence includes: Anastomotic - positive cytology or biopsy; Abdominal, pelvic and retroperitoneal nodes - progressively enlarging node as evidenced by 2 CT scans separated by at least a 4 week interval, ureteral obstruction in the presence of a mass as documented on CT scan; Peritoneum - positive cytology or biopsy, progressively enlarged intraperitoneal solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Ascites - positive cytology or biopsy; Liver - positive cytology or biopsy; Pelvic mass - positive cytology or biopsy, progressively enlarging intrapelvic solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Abdominal wall - positive cytology or biopsy; Lung - positive cytology or biopsy or presence of multiple pulmonary nodules; Bone marrow - positive cytology, aspiration or biopsy.

Secondary Outcome Measures

Full Information

NCT ID

NCT00002842

First Posted

November 1, 1999

Last Updated

February 28, 2017

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00002842

Brief Title

Liver Resection and Floxuridine Plus Fluorouracil and Leucovorin in Treating Patients With Liver Metastases From Colorectal Cancer

Official Title

Hepatic Resection Followed by Concurrent Adjuvant Portal Vein Infusion of Fluorodeoxyuridine and Systemic 5-Fluorouracil and Folinic Acid for Metastatic Colorectal Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

September 1994 (undefined)

Primary Completion Date

May 2014 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving drugs in different ways may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of surgery followed by floxuridine plus systemic fluorouracil and leucovorin in treating patients with liver metastases from colorectal cancer.

Detailed Description

OBJECTIVES: Evaluate the efficacy of hepatic resection followed by portal vein infusion of floxuridine plus systemic fluorouracil/leucovorin calcium in patients with metastatic colorectal cancer. Study the toxic effects of adjuvant chemotherapy following hepatic resection. Evaluate mRNA expression of enzymes that may be important to the cytotoxicity of fluoropyrimidines in tumor cells, including thymidylate synthase, ribonucleotide reductase, and folylglutamyl synthetase, by polymerase chain reaction and immunohistochemistry. OUTLINE: Following resection of the liver and all extrahepatic colorectal cancer, patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks. If biopsy-proven metastatic disease develops, treatment may be stopped at the investigator's discretion. Continuation of regional therapy should be considered for extrahepatic failure. No concurrent radiotherapy is permitted. Patients are followed every 3 months for 3 years, then every 6 months for survival. PROJECTED ACCRUAL: It is expected that 50 patients will be entered over approximately 5 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Colorectal Cancer, Metastatic Cancer

Keywords

stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, liver metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

49 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin

Arm Type

Experimental

Arm Description

Patients receive floxuridine via portal vein infusion from days 1-14. Systemic chemotherapy consists of leucovorin calcium on days 8-14 and fluorouracil on days 9-13. Courses repeat every 4 weeks for a total of 12 weeks

Intervention Type

Drug

Intervention Name(s)

floxuridine

Intervention Description

Starting dose of 0.2 mg/kg/day for 14 consecutive days.

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Intervention Description

300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Intervention Description

500 mg/m2/day by continuous intravenous infusion beginning 24 hours prior to the first dose of 5-FU and continuing until 12 hours following the last dose of 5-FU.

Intervention Type

Procedure

Intervention Name(s)

adjuvant therapy

Intervention Description

Chemotherapy given after hepatic resection

Intervention Type

Procedure

Intervention Name(s)

conventional surgery

Intervention Description

Hepatic resection

Primary Outcome Measure Information:

Title

2 Year Disease-free Survival .

Description

Estimated using the product-limit method of Kaplan and Meier. Disease free survival, defined as first documented evidence of treatment failure. Acceptable evidence includes: Anastomotic - positive cytology or biopsy; Abdominal, pelvic and retroperitoneal nodes - progressively enlarging node as evidenced by 2 CT scans separated by at least a 4 week interval, ureteral obstruction in the presence of a mass as documented on CT scan; Peritoneum - positive cytology or biopsy, progressively enlarged intraperitoneal solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Ascites - positive cytology or biopsy; Liver - positive cytology or biopsy; Pelvic mass - positive cytology or biopsy, progressively enlarging intrapelvic solid mass as evidenced by 2 CT scans separated by at least 4 weeks; Abdominal wall - positive cytology or biopsy; Lung - positive cytology or biopsy or presence of multiple pulmonary nodules; Bone marrow - positive cytology, aspiration or biopsy.

Time Frame

2 years after treatment

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

DISEASE CHARACTERISTICS: Histologically confirmed colorectal carcinoma or radiologically confirmed colorectal carcinoma in a synchronous metastasis Intrahepatic metastases required No more than 15 metastases involving no more than 60% of functioning liver No extrahepatic disease unless: Resectable anastomotic or locally recurrent tumor Resectable mesenteric lymph node involvement in patients undergoing initial resection of primary colorectal carcinoma Disease extension from liver metastasis amenable to en bloc resection (e.g., diaphragm wall, kidney, abdominal wall) No biopsy-proven chronic active hepatitis PATIENT CHARACTERISTICS: Age: Physiologic 18 to 70 Performance status: Karnofsky 60%-100% Hematopoietic: AGC at least 1,500 Platelets at least 100,000 Hepatic: Bilirubin no greater than 2.0 mg/dL (unless reversibly obstructed by metastasis) Renal: Creatinine no greater than 2.0 mg/dL Other: No second malignancy within 5 years except adequately treated: Nonmelanomatous skin cancer In situ bladder cancer In situ cervical cancer No pregnant women PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Prior mitomycin or nitrosoureas allowed Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the liver At least 3 weeks since radiotherapy and recovered Prior pelvic radiotherapy allowed No planned concurrent radiotherapy Surgery: Not specified

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lucille A. Leong, MD

Organizational Affiliation

City of Hope Comprehensive Cancer Center

Official's Role

Study Chair

Facility Information:

Facility Name

City of Hope Comprehensive Cancer Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010-3000

Country

United States

Colorectal Cancer, Metastatic Cancer

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial