TerminatedNCT00002525Updated Jun 28, 2023Results posted

Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed

A Phase 3 interventional study of fluorouracil and leucovorin calcium in Colorectal Cancer, sponsored by ECOG-ACRIN Cancer Research Group. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-06-28.

Sponsored by ECOG-ACRIN Cancer Research Group · Phase 3, Interventional, and Treatment

Why this study was terminated

The study was stopped before reaching its accrual goal due to slow accrual

From the registry’s dates

Registered 6 years 1 month after the study started (first participant enrolled Oct 1993, registered Nov 1999).

Phase: Phase 3
Study type: Interventional
Enrollment: 859
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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. It is not yet known if surgery is more effective with or without chemotherapy for colon cancer.

PURPOSE: Randomized phase III trial to evaluate whether perioperative 5-Fluorouracil (5-FU) chemotherapy after curative resection could improve overall survival and disease-free survival in patients with Duke's B3 or C colon cancer.

Read the detailed description

OBJECTIVES:

I. To determine if adjuvant therapy with one week of continuous 5-FU given within 24 hours of a curative colon resection followed by 6 months of 5-FU/leucovorin is effective in prolonging the disease-free survival and increasing overall survival in patients with Dukes' B3 or C colon cancer, when compared to patients who are treated with 5-FU/leucovorin only.

II. 1. To determine if a week of perioperative continuous 5-FU affects disease-free survival and overall survival in patients with Dukes' B2 colon cancer.

OUTLINE: This is an open-label, randomized phase III study. Patients undergo curative colon resection via laparotomy. Patients are randomized to 1 of 2 arms in a 1:1 ratio.

Arm I (Perioperative 5-FU): Within 24 hours of the colon resection, patients receive perioperative 5-fluorouracil (5-FU) intravenously (IV) over 24 hours for 7 days.

Arm II (No perioperative 5-FU): Patients receive no perioperative fluorouracil.

After surgery, patients with stage I, stage IIA, or stage IV colon cancer are immediately removed from study. Patients with stage IIB, IIC, or III colon cancer are re-registered within 35 days postoperatively. Beginning 21-35 days after surgery, patients with stage IIC or III disease receive leucovorin calcium IV bolus immediately followed by 5-FU IV bolus on days 1-5. Courses repeat every 28 days for a total of 6 courses in the absence of disease progression or unacceptable toxicity. Patients with stage IIB disease do not receive adjuvant 5-FU and leucovorin calcium.

Patients are followed every 3 months for 2 years, then every 6 months for 2 years, and then annually until 15 years.

PROJECTED ACCRUAL: A total of 800-2,000 patients (at least 400 per treatment arm) will be accrued for this study over 2-3 years.

Conditions studied

Colorectal Cancer

Browse trials for

Colonic Neoplasms 1,432

Keywords

stage II colon cancer
stage III colon cancer

In context

Colonic Neoplasms

1,432 studies on the registry are indexed under Colonic Neoplasms; 357 are open to participants now.

This study's enrollment of 859 is above the median of 90 across 1,034 interventional studies indexed under Colonic Neoplasms.

Browse Colonic Neoplasms studies →

Lead sponsor

ECOG-ACRIN Cancer Research Group is the lead sponsor of 118 studies on the registry; 13 are open to participants now.

Of its 13 completed or terminated interventional studies of FDA-regulated products, 13 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility Criteria for Randomization:

Inclusion criteria

Inclusion Criteria:

Adenocarcinoma of the colon documented by colonoscopy or barium enema
Tumor either considered resectable or totally resected within 24 hours prior to study
Randomization within 2 weeks prior to surgery or within 24 hours after surgery required
Patients randomized after surgery must meet the following criteria:
- Complete resection performed with no evidence of residual disease or distant metastases
- Distal margin of tumor above the peritoneal reflection in area of rectum
- No free perforation Intestinal obstruction allowed
- Preliminary or complementary colostomy allowed
Concurrent registration for E3293 strongly recommended
Age 18 and over
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Adequate organ function based on the following tests within 2 weeks prior to randomization
- White Blood Cell (WBC) at least 3,000/mm\^3
- Platelet count at least 100,000/mm\^3
- Bilirubin no greater than 2.0 mg/dL
- Creatinine no greater than 2.0 mg/dL
No second malignancy within 5 years except: superficial non-melanomatous skin cancer and carcinoma in situ of the cervix
Fertile patients must use adequate contraception

Exclusion criteria

Exclusion Criteria:

Dual primary tumors
Prior nonmalignant systemic disease that would preclude use of chemotherapy
Pregnant or nursing
Prior fluorouracil
Other prior or concurrent chemotherapy for this malignancy
Prior or concurrent radiotherapy for this malignancy

Eligibility Criteria for Re-registration for Patients Randomized Pre-operatively:

Must have pathologic classification of Dukes' B2, B3, or C disease by the contributing institution.
Must be re-registered \< 35 days after surgery.
ECOG performance status of 0-2.
Complete resection must have been performed with no evidence of residual disease or distant metastasis.
Distal margin of the tumor must not extend below the peritoneal reflection in the area of the rectum.
Single primary colon carcinoma without free perforation demonstrated. Patients with intestinal obstruction are eligible. Preliminary or complementary colostomy dose not preclude entry of a patient.
Have WBC > 3000/mm\^3, platelets > 100,000/mm\^3, adequate renal (serum creatinine \<= 2.0mg/dL) and hepatic function (bilirubin \<= 2.0mg/dL), within one week prior to beginning adjuvant chemotherapy (For Dukes' B3 and C patients only).

Eligibility Criteria for Re-registration for Patients Randomized Post-operatively:

Must have pathologic classification of Dukes' B2, B3, or C disease by the contributing institution.
Patient must be re-registered \< 35 days after surgery.
ECOG performance status of 0-2.
Started perioperative 5-FU, if assigned, within 24 hours of surgery.
Have WBC > 3000/mm\^3, platelets > 100,000/mm\^3, adequate renal (serum creatinine \<= 2.0mg/dL) and hepatic function (bilirubin \< =2.0mg/dL), within one week prior to beginning adjuvant chemotherapy (For Dukes' B3 and C patients only).

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 859 participants (actual)

Study arms

Experimental
Perioperative 5-FU
Within 24 hours of the colon resection, patients receive perioperative fluorouracil intravenously (IV) over 24 hours for 7 days. After surgery (beginning 21-35 days post-surgery), 5-FU was given at a dose of 425 mg/m\^2 IV push on days 1-5, and leucovorin calcium was given at a dose of 20mg/m\^2 IV push on days 1-5
Drug: fluorouracil · Drug: leucovorin calcium
Active comparator
No perioperative 5-FU
Patients receive no perioperative fluorouracil. After surgery (beginning 21-35 days post-surgery), 5-FU was given at a dose of 425 mg/m\^2 IV push on days 1-5, and leucovorin calcium was given at a dose of 20mg/m\^2 IV push on days 1-5
Drug: fluorouracil · Drug: leucovorin calcium

Interventions

Drugfluorouracil
Perioperative 5-FU: 600 mg/m\^2/d x 7 days continuous IV, beginning within 24 hours of surgery After surgery, 5-FU was given 425 mg/m\^2 IV push on days 1-5
Also known as: 5-FU, Adrucil, Efudex
Drugleucovorin calcium
given after surgery at dose of 20mg/m\^2 IV push on days 1-5
Also known as: Leucovorin, Wellcovorin, Citrovorum factor, Folinic acid, 5-formyl tetrahydrofolate, LV, LCV

What researchers measure

Primary outcomes

5-year Overall Survival Rate in Patients With Dukes' B3/C Disease
Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. Kaplan-Meier method was used to estimate 5-year OS rate
Time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization

Secondary outcomes

5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease
Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer, or deaths, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Patients without any follow up data were censored at random assignment. Kaplan-Meier method was used to estimate the 5-year DFS rate.
Time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
5-year Overall Survival Rate in Patients With Dukes' B2 Disease
Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. Kaplan-Meier method was used to estimate 5-year OS rate
Time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease
Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer, or deaths, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Patients without any follow up data were censored at random assignment. Kaplan-Meier method was used to estimate the 5-year DFS rate.
Time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization

Results

Posted Jul 20, 2016

Participant flow

This study was activated on August 20, 1993 and was terminated on May 19, 2000 before reaching its accrual goal due slow accrual. The first accrual was on October 1, 1993. The final accrual for the study was 859 patients.

Participant flow — Overall Study
Milestone	Perioperative 5-FU	No Perioperative 5-FU
Started	427	428
Treated	419	0
Dukes' b3 or c stage	156	158
Dukes' b2 stage	150	139
Completed	241	428
Not completed	186	0
Withdrew: Adverse event	36	0
Withdrew: Death	5	0
Withdrew: Withdrawal by subject	11	0
Withdrew: Start non-protocol therapy	1	0
Withdrew: Other complicating disease	1	0
Withdrew: Duke's a, b1, d disease	92	0
Withdrew: Error	6	0
Withdrew: Other	26	0
Withdrew: Never start protocol therapy	8	0

Outcome measures

Primary5-year Overall Survival Rate in Patients With Dukes' B3/C Disease

Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. Kaplan-Meier method was used to estimate 5-year OS rate

Time frame:: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Reported as:: Number · proportion of participants

5-year Overall Survival Rate in Patients With Dukes' B3/C Disease
proportion of participants	Perioperative 5-FU	No Perioperative 5-FU
5-year Overall Survival Rate in Patients With Dukes' B3/C Disease	0.666 (0.585 to 0.735)	0.612 (0.530 to 0.683)

Statistical analysis

Perioperative 5-FU vs No Perioperative 5-FU · Log Rank · p = 0.178 (one-sided log-rank test p value)

Secondary5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease

Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer, or deaths, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Patients without any follow up data were censored at random assignment. Kaplan-Meier method was used to estimate the 5-year DFS rate.

Time frame:: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Reported as:: Number · proportion of participants

5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease
proportion of participants	Perioperative 5-FU	No Perioperative 5-FU
5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease	0.582 (0.486 to 0.668)	0.543 (0.442 to 0.634)

Statistical analysis

Perioperative 5-FU vs No Perioperative 5-FU · Log Rank · p = 0.847 (two-sided log rank test)

Secondary5-year Overall Survival Rate in Patients With Dukes' B2 Disease

Overall survival (OS) is defined as time from randomization to death from any cause or last date known alive. Kaplan-Meier method was used to estimate 5-year OS rate

Time frame:: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Reported as:: Number · proportion of participants

5-year Overall Survival Rate in Patients With Dukes' B2 Disease
proportion of participants	Perioperative 5-FU	No Perioperative 5-FU
5-year Overall Survival Rate in Patients With Dukes' B2 Disease	0.851 (0.783 to 0.899)	0.780 (0.701 to 0.841)

Secondary5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease

Time frame:: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Reported as:: Number · proportion of participants

5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease
proportion of participants	Perioperative 5-FU	No Perioperative 5-FU
5-year Disease-free Survival Rate in Patients With Dukes' B2 Disease	0.749 (0.660 to 0.818)	0.724 (0.626 to 0.801)

Adverse events

Collected over Patients on Arm I received perioperative 5-FU, patients on Arm II received no perioperative chemotherapy. AEs, however, were reported for all patients and assessed at the end of treatment and 30 days after the last dose of the therapy.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Arm I (Perioperative 5-FU)	—	75/418 (17.9%)	236/418 (56.5%)
Arm II (No Perioperative 5-FU)	—	4/422 (0.9%)	9/422 (2.1%)
Adjuvant Chemotherapy-- 5-FU+Levamisolem	—	76/171 (44.4%)	167/171 (97.7%)
Adjuvant Chemotherapy-- 5-FU+Leucovovin	—	32/61 (52.5%)	58/61 (95.1%)

Most frequent serious events

Showing 10 of 20

Most frequent serious events
Event	Arm I (Perioperative 5-FU)	Arm II (No Perioperative 5-FU)	Adjuvant Chemotherapy-- 5-FU+Levamisolem	Adjuvant Chemotherapy-- 5-FU+Leucovovin
DiarrheaGastrointestinal disorders	14/418	0/422	20/171	15/61
StomatitisGastrointestinal disorders	11/418	0/422	6/171	9/61
LeukopeniaInvestigations	3/418	1/422	23/171	8/61
OthersGeneral disorders	0/418	2/422	7/171	6/61
Nausea/VomitingGastrointestinal disorders	7/418	0/422	8/171	4/61
Neuro-motorNervous system disorders	6/418	0/422	1/171	4/61
AnemiaBlood and lymphatic system disorders	22/418	0/422	1/171	1/61
InfectionInfections and infestations	9/418	0/422	1/171	3/61
SkinSkin and subcutaneous tissue disorders	2/418	0/422	3/171	3/61
Neuro-clinicalNervous system disorders	0/418	0/422	6/171	3/61

Most frequent other events

Showing 10 of 13

Most frequent other events
Event	Arm I (Perioperative 5-FU)	Arm II (No Perioperative 5-FU)	Adjuvant Chemotherapy-- 5-FU+Levamisolem	Adjuvant Chemotherapy-- 5-FU+Leucovovin
AnemiaBlood and lymphatic system disorders	209/418	7/422	105/171	43/61
Nausea/vomitingGastrointestinal disorders	116/418	4/422	94/171	27/61
LeukopeniaInvestigations	25/418	2/422	78/171	32/61
Neuro-clinicalNervous system disorders	21/418	1/422	84/171	18/61
DiarrheaGastrointestinal disorders	67/418	3/422	74/171	27/61
SkinSkin and subcutaneous tissue disorders	39/418	2/422	73/171	24/61
ThrombocytopeniaInvestigations	24/418	0/422	66/171	14/61
StomatitisGastrointestinal disorders	71/418	1/422	59/171	20/61
VomitingGastrointestinal disorders	60/418	3/422	45/171	11/61
InfectionInfections and infestations	0/418	0/422	33/171	9/61

Baseline characteristics

The primary analysis population for the study was all randomized patients with Duke's B3 and C disease.

Age, Continuous
Age, Continuous(Years)	Perioperative 5-FU	No Perioperative 5-FU	Total
Median	63 (30 to 89)	66 (25 to 86)	65 (25 to 89)

Sex/Gender, Customized
Sex/Gender, Customized(participants)	Perioperative 5-FU	No Perioperative 5-FU	Total
Female	57	61	118
Male	99	96	195

Study locations

1 site

Loyola University Medical Center
Maywood, Illinois 60153, United States

References and documents

Publications

Kemeny M, Ibrahim J, Benson AB, et al.: Post-operative complications of continuous infusion 5 FU following curative resection of colon cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A923, 260a, 1997.

Individual participant data

Plan to share: Yes — Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Jun 28, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00002525
Lead sponsor: ECOG-ACRIN Cancer Research Group
Collaborators: National Cancer Institute (NCI), SWOG Cancer Research Network, Cancer and Leukemia Group B, American College of Surgeons, NSABP Foundation Inc
Responsible party: Sponsor
First posted: Apr 6, 2004
Start date: Oct 1, 1993
Primary completion: Feb 2015
Completion: Apr 2015
Results posted: Jul 20, 2016
Last update: Jun 28, 2023

Study contacts

Mary M. Kemeny, MD, FACS

study chair · SUNY at Stony Brook

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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