Colorectal CancerPhase 3NCT00002525
Perioperative Chemotherapy in Treating Patients With Colon Cancer That Can Be Surgically Removed
A Phase 3 study testing fluorouracil and leucovorin calcium in people with Colorectal Cancer, run by ECOG-ACRIN Cancer Research Group at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- fluorouracil and leucovorin calcium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 859 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 1993to Apr 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
United States1 site
Loyola University Medical Center
Maywood, Illinois, 60153
About this study
Official title: Phase III Intergroup Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection, Followed by 5-FU/Leucovorin for Patients With Colon Cancer
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:
- 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
- Colorectal Cancer
- Being tested
- fluorouracil, leucovorin calcium
- Keywords
- stage II colon cancer, stage III colon cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluorouracilDrug
Also called 5-FU, Adrucil, Efudex
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 called Leucovorin, Wellcovorin, Citrovorum factor, Folinic acid
given after surgery at dose of 20mg/m^2 IV push on days 1-5
| Study group | Role | What they receive |
|---|---|---|
| Perioperative 5-FU | Experimental | 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 Receives: Drug: fluorouracil; Drug: leucovorin calcium |
| No perioperative 5-FU | Active comparator | 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 Receives: Drug: fluorouracil; Drug: leucovorin calcium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Secondary outcomes (3)
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.
Measured: 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
Measured: 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.
Measured: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2004 (estimated)
- Study start1 Oct 1993
- Primary completionFeb 2015
- Study completionApr 2015
Why it stopped: The study was stopped before reaching its accrual goal due to slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by ECOG-ACRIN Cancer Research GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 859 participants (actual)
Sponsor and investigators
- Lead sponsor
- ECOG-ACRIN Cancer Research Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI), SWOG Cancer Research Network, Cancer and Leukemia Group B, American College of Surgeons, NSABP Foundation Inc
- Responsible party
- Sponsor
- Investigators
- Mary M. Kemeny, MD, FACS, Study chair, SUNY at Stony Brook
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00002525
- Sponsor's protocol ID
- E1292
- Other IDs
- E1292, U10CA023318, CDR0000078337
- Status last verified
- Jun 2023
- First submitted
- 1 Nov 1999
- Last updated
- 28 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Intergroup Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection, Followed by 5-FU/Leucovorin for Patients With Colon Cancer
- ClinicalTrials.gov ID
- NCT00002525
- Acronym / sponsor ID
- E1292
- Conditions
- Colorectal Cancer
- Keywords
- stage II colon cancer, stage III colon cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped before reaching its accrual goal due to slow accrual
- Enrolment
- 859 participants (actual)
- Lead sponsor
- ECOG-ACRIN Cancer Research GroupResearch network
- Collaborators
- National Cancer Institute (NCI), SWOG Cancer Research Network, Cancer and Leukemia Group B, American College of Surgeons, NSABP Foundation Inc
- Study start
- 1 Oct 1993 (actual)
- Primary completion
- Feb 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 6 Apr 2004 (estimated)
- Results
- Posted 20 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Perioperative 5-FU | Experimental | Drug: fluorouracil, Drug: leucovorin calciumWithin 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 |
| No perioperative 5-FU | Active comparator | Drug: fluorouracil, Drug: leucovorin calciumPatients 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
- Concurrent registration for E3293 strongly recommended
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fluorouracilAlso: 5-FU, Adrucil, EfudexPerioperative 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 | Drug | No perioperative 5-FU, Perioperative 5-FU |
| leucovorin calciumAlso: Leucovorin, Wellcovorin, Citrovorum factor, Folinic acidgiven after surgery at dose of 20mg/m^2 IV push on days 1-5 | Drug | No perioperative 5-FU, Perioperative 5-FU |
Primary outcome
5-year Overall Survival Rate in Patients With Dukes' B3/C Disease
Time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
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
3 secondary outcomes
5-year Disease-free Survival Rate in Patients With Dukes' B3/C Disease
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
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
Time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationKemeny 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 dataSharing planned: Yes. Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mary M. Kemeny, MD, FACS study chair
SUNY at Stony Brook
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fluorouracil and leucovorin calcium in people with Colorectal Cancer, run by ECOG-ACRIN Cancer Research Group at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Jul 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
5-year Overall Survival Rate in Patients With Dukes' B3/C Disease (time frame: every 3 months for 2 years, then every 6 months for 2 years, and then annually until year 15 after randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00002525, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2023.