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Liver Infusions of Fluorouracil in Treating Patients With Dukes' A, Dukes' B, or Dukes' C Colon Cancer Undergoing Surgery

Primary Purpose

Colorectal Cancer

Status

Completed

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

fluorouracil

Observation

sodium heparin

About this trial

This is an interventional treatment trial for Colorectal Cancer focused on measuring stage I colon cancer, stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon

Eligibility Criteria

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

Inclusion Criteria:

more than one synchronous primary colon tumor
white blood cell (WBC) > 4000/cu.mm. and platelet count greater than or equal to 100,000/cu.mm.
evidence of adequate renal (serum creatinine less than or equal to 1.5 mg%) and hepatic function (bilirubin less than or equal to 1.5 mg%; serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 60 I.U./ml)
performance status of 0, 1 or 2
Patients with intestinal obstruction are eligible. Preliminary or complementary colostomy does not preclude entry of a patient provided randomization is carried out prior to the planned curative resection.
The distal margin of the tumor must be greater than or equal to 12 cm from the anal verge as endoscopically measured with the patient in the knee-chest position.
Carcinoembryonic antigen (CEA) must be performed pre-operatively but results need not be known at the time of randomization.

Exclusion criteria:

malignant colon tumors other than carcinoma, i.e., sarcoma, lymphoma, etc.
patients whose tumors demonstrate free perforation
previous or concomitant malignancy, regardless of site - except patients with squamous or basal cell carcinoma of the skin, and carcinoma in situ of the cervix which have been adequately treated
patients who have received prior treatment other than preliminary or complementary colostomy (radiation, chemotherapy or surgery) for their current malignancy.
patients having tumors within 12 cm of the anal verge
performance status of 3 or 4
patients having non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) which would preclude their being subject to the chemotherapy treatment option
patients who are pregnant at the time of randomization
patients with psychiatric or addictive disorders which would preclude obtaining informed consent
patients who have multiple primary tumors involving both the colon and the rectum which would preclude them from being classified as having only colon cancer or only rectal cancer

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm 1: Postoperative 5 FU + sodium heparin

Arm 2: Postoperative observation

Arm Description

Continuous portal vein infusion with 5 FU 600 mg/m2 + 5000 units sodium heparin per day given for a total of 7 consecutive days.

Outcomes

Primary Outcome Measures

Disease free interval

Evidence of treatment failure (presence of tumor in local/regional or distant sites, confirmed by either biopsy or other acceptable evidence.

Survival

Secondary Outcome Measures

Full Information

NCT ID

NCT00427310

First Posted

January 18, 2007

Last Updated

December 31, 2012

Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI), Northern California Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT00427310

Brief Title

Liver Infusions of Fluorouracil in Treating Patients With Dukes' A, Dukes' B, or Dukes' C Colon Cancer Undergoing Surgery

Official Title

A Clinical Trial to Evaluate the Postoperative Portal Vein Infusion of 5-Fluorouracil and Heparin in Patients With Resectable Adenocarcinoma of the Colon

Study Type

Interventional

2. Study Status

Record Verification Date

December 2012

Overall Recruitment Status

Completed

Study Start Date

March 1984 (undefined)

Primary Completion Date

September 1989 (Actual)

Study Completion Date

February 2001 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

NSABP Foundation Inc

Collaborators

National Cancer Institute (NCI), Northern California Cancer Center

4. Oversight

5. Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving fluorouracil into the liver is more effective than no further treatment for patients with colon cancer undergoing surgery. PURPOSE: This randomized phase III trial is studying giving infusions of fluorouracil into the liver in treating patients with Dukes' A, Dukes' B, or Dukes' C colon cancer undergoing surgery.

Detailed Description

OBJECTIVES: Determine whether adjuvant therapy with portal hepatic perfusion of 5-fluorouracil and sodium heparin effectively prolongs the disease-free interval and increases survival in patients undergoing curative resection of adenocarcinoma of the colon. OUTLINE: Randomized study. Patients are randomized preoperatively; those randomized to Arm 1 begin therapy intraoperatively or within 6 hours of colonic resection. Arm 1: 5-Fluorouracil plus sodium heparin. Those randomized to Arm 2 receive no adjuvant therapy. Arm 2: observation (no further treatment). PROJECTED ACCRUAL: 1,334 patients will be entered over a 4-year period.

6. Conditions and Keywords

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

Colorectal Cancer

Keywords

stage I colon cancer, stage II colon cancer, stage III colon cancer, adenocarcinoma of the colon

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1158 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1: Postoperative 5 FU + sodium heparin

Arm Type

Experimental

Arm Description

Continuous portal vein infusion with 5 FU 600 mg/m2 + 5000 units sodium heparin per day given for a total of 7 consecutive days.

Arm Title

Arm 2: Postoperative observation

Arm Type

Active Comparator

Intervention Type

Drug

Intervention Name(s)

fluorouracil

Other Intervention Name(s)

5 FU

Intervention Type

Other

Intervention Name(s)

Observation

Intervention Type

Drug

Intervention Name(s)

sodium heparin

Primary Outcome Measure Information:

Title

Disease free interval

Description

Evidence of treatment failure (presence of tumor in local/regional or distant sites, confirmed by either biopsy or other acceptable evidence.

Time Frame

From randomization up to 4 years.

Title

Survival

Time Frame

From randomization up to 4 years.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: more than one synchronous primary colon tumor white blood cell (WBC) > 4000/cu.mm. and platelet count greater than or equal to 100,000/cu.mm. evidence of adequate renal (serum creatinine less than or equal to 1.5 mg%) and hepatic function (bilirubin less than or equal to 1.5 mg%; serum glutamic oxaloacetic transaminase (SGOT) less than or equal to 60 I.U./ml) performance status of 0, 1 or 2 Patients with intestinal obstruction are eligible. Preliminary or complementary colostomy does not preclude entry of a patient provided randomization is carried out prior to the planned curative resection. The distal margin of the tumor must be greater than or equal to 12 cm from the anal verge as endoscopically measured with the patient in the knee-chest position. Carcinoembryonic antigen (CEA) must be performed pre-operatively but results need not be known at the time of randomization. Exclusion criteria: malignant colon tumors other than carcinoma, i.e., sarcoma, lymphoma, etc. patients whose tumors demonstrate free perforation previous or concomitant malignancy, regardless of site - except patients with squamous or basal cell carcinoma of the skin, and carcinoma in situ of the cervix which have been adequately treated patients who have received prior treatment other than preliminary or complementary colostomy (radiation, chemotherapy or surgery) for their current malignancy. patients having tumors within 12 cm of the anal verge performance status of 3 or 4 patients having non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) which would preclude their being subject to the chemotherapy treatment option patients who are pregnant at the time of randomization patients with psychiatric or addictive disorders which would preclude obtaining informed consent patients who have multiple primary tumors involving both the colon and the rectum which would preclude them from being classified as having only colon cancer or only rectal cancer

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Norman Wolmark, MD

Organizational Affiliation

NSABP Foundation Inc

Official's Role

Principal Investigator

12. IPD Sharing Statement

Citations:

PubMed Identifier

20679606

Citation

O'Connell MJ, Lavery I, Yothers G, Paik S, Clark-Langone KM, Lopatin M, Watson D, Baehner FL, Shak S, Baker J, Cowens JW, Wolmark N. Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. J Clin Oncol. 2010 Sep 1;28(25):3937-44. doi: 10.1200/JCO.2010.28.9538. Epub 2010 Aug 2.

Results Reference

background

PubMed Identifier

20082144

Citation

Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05. A baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. doi: 10.1245/s10434-009-0881-y.

Results Reference

background

Citation

Wilkinson NW, Yothers G, Lopa SH, et al.: Long-term survival results of surgery alone compared with surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP adjuvant trials C-01 through C-05. [Abstract] American Society of Clinical Oncology 2009 Gastrointestinal Cancers Symposium, 15-17 January 2009, San Francisco, CA. A-442, 2009.

Results Reference

background

PubMed Identifier

17228023

Citation

Kim GP, Colangelo LH, Wieand HS, Paik S, Kirsch IR, Wolmark N, Allegra CJ; National Cancer Institute. Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol. 2007 Mar 1;25(7):767-72. doi: 10.1200/JCO.2006.05.8172. Epub 2007 Jan 16.

Results Reference

background

Citation

Kim GP, Colangelo L, Wieand H, et al.: Prognostic and predictive roles of high-degree microsatellite instability (MSI-H) in colon cancer: National Cancer Institute (NCI)-National Surgical Adjuvant Bowel Project (NSABP) collaborative study. [Abstract] American Society of Clinical Oncology 2005 Gastrointestinal Cancers Symposium, 27-29 January 2005, Miami, Florida. A-227, 2005.

Results Reference

background

PubMed Identifier

12525515

Citation

Allegra CJ, Paik S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG, Wolmark N, Wieand HS. Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes' B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. J Clin Oncol. 2003 Jan 15;21(2):241-50. doi: 10.1200/JCO.2003.05.044.

Results Reference

background

PubMed Identifier

11273592

Citation

Wolmark N, Colangelo L, Wieand S. National Surgical Adjuvant Breast and Bowel Project trials in colon cancer. Semin Oncol. 2001 Feb;28(1 Suppl 1):9-13. doi: 10.1016/s0093-7754(01)90245-3.

Results Reference

background

PubMed Identifier

10564677

Citation

Dignam JJ, Colangelo L, Tian W, Jones J, Smith R, Wickerham DL, Wolmark N. Outcomes among African-Americans and Caucasians in colon cancer adjuvant therapy trials: findings from the National Surgical Adjuvant Breast and Bowel Project. J Natl Cancer Inst. 1999 Nov 17;91(22):1933-40. doi: 10.1093/jnci/91.22.1933.

Results Reference

background

PubMed Identifier

10334518

Citation

Mamounas E, Wieand S, Wolmark N, Bear HD, Atkins JN, Song K, Jones J, Rockette H. Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol. 1999 May;17(5):1349-55. doi: 10.1200/JCO.1999.17.5.1349.

Results Reference

background

Citation

Wolmark N, Rockette H, Petrelli N, et al.: Long-term results of the efficacy of perioperative portal vein infusion of 5-FU for treatment of colon cancer: NSABP C-02. [Abstract] Proceedings of the American Society of Clinical Oncology 13: A-561, 194, 1994.

Results Reference

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Liver Infusions of Fluorouracil in Treating Patients With Dukes' A, Dukes' B, or Dukes' C Colon Cancer Undergoing Surgery

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