Colorectal Cancer, Metastatic Cancer
Conditions
Keywords
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer, liver metastases
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.
Interventions
DRUGfloxuridine
Starting dose of 0.2 mg/kg/day for 14 consecutive days.
DRUGfluorouracil
300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.
DRUGleucovorin calcium
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.
PROCEDUREadjuvant therapy
Chemotherapy given after hepatic resection
PROCEDUREconventional surgery
Hepatic resection
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2 Year Disease-free Survival . | 2 years after treatment | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin 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
floxuridine: Starting dose of 0.2 mg/kg/day for 14 consecutive days.
fluorouracil: 300 mg/m2/day by intravenous bolus 24 hours apart for 5 consecutive days.
leucovorin calcium: 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.
adjuvant therapy: Chemotherapy given after hepatic resection
conventional surgery: Hepatic resection | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | ineligible for surgical resection | 27 |
Baseline characteristics
| Characteristic | Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin |
|---|---|
| Age, Continuous | 56 years |
| Region of Enrollment United States | 22 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 22 |
| serious Total, serious adverse events | 8 / 22 |
Outcome results
Primary
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.
Time frame: 2 years after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Hepatic Resection/Portal Vein FUdr/Systemic 5-FU & Leucovorin | 2 Year Disease-free Survival . | 9 percentage of participants |