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Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer

Primary Purpose

Stage II Colon Cancer, Stage III Colon Cancer

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
leucovorin calcium
fluorouracil
oxaliplatin
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stage II Colon Cancer

Eligibility Criteria

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

Inclusion Criteria: Patients must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines In the opinion of the investigator, patients must have a 10-year life expectancy, excluding their diagnosis of cancer The interval between curative resection and randomization must be no more than 42 days The distal extent of the tumor must be >= 12 cm from the anal verge on endoscopy Patients must have colonic adenocarcinoma that meets one of the criteria below: Stage II carcinoma (T3, 4; N0; M0) - The tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues (T3) or directly invades other organs or structures, and/or perforates visceral peritoneum (T4), excluding free perforation Stage III carcinoma (any T; N1, 2; M0) - The tumor has invaded to any depth, with involvement of regional lymph nodes AGCs >= 1500/mm^3 Platelets >= 100,000/mm^3 Bilirubin within or below the normal limits for the laboratory Alkaline phosphatase within or below the normal limits for the laboratory SGOT or SGPT within or below the normal limits for the laboratory Serum creatinine within or below the normal limits for the laboratory Patients with more than one synchronous primary colon tumor are eligible; for the purpose of this protocol, staging classification will be based on the stage of the more advanced primary tumor Patients are eligible if adjacent structures (e.g., bladder, small intestine, ovary, etc.) involved by direct extension of the primary tumor are removed en bloc and if, in the judgement of the surgeon and by confirmation on histological examination (i.e., margins of resection are not involved), the resection is deemed to be "curative" Patients must have an ECOG performance status of 0, 1, or 2 Patients with intestinal obstruction are eligible; preliminary or complementary colostomy does not preclude entry Patients with prior noncolorectal malignancies are eligible if they have been disease-free for >= 5 years; patients with squamous or basal cell carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by operation only, or lobular carcinoma in situ of the breast are eligible, even if these conditions were diagnosed within 5 years prior to randomization Exclusion Criteria: Prior invasive colon or rectal malignancy, regardless of disease-free interval Current or past malignant colon tumors other than carcinoma, i.e., sarcoma, lymphoma, carcinoid, etc., regardless of disease-free interval Tumors located < 12 cm from the anal verge on preoperative endoscopy Tumors that demonstrate free perforation as manifested by free air or free fluid in the abdomen; patients with walled-off perforation are eligible Pregnancy or lactation at the time of proposed randomization; (5-FU and oxaliplatin are both teratogenic and mutagenic and may cause fetal harm;) eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods Noncurative surgical resection or prior chemotherapy or radiotherapy for this malignancy, with the exception of a decompressing colostomy Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient's receiving either chemotherapy treatment option; specifically excluded are patients with active ischemic heart disease (class III or class IV myocardial disease -- New York Heart Association) or a recent history of myocardial infarction (within 6 months), or current symptomatic arrhythmia Class III: Patients with cardiac disease resulting in marked limitation of physical activity; such patients are comfortable at rest; less-than-ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain Class IV: Patients with cardiac disease resulting in inability to perform any physical activity without discomfort; symptoms of cardiac insufficiency or the anginal syndrome may be present even at rest Psychiatric or addictive disorders that would preclude obtaining informed consent Multiple primary tumors involving both the colon and the rectum that would preclude the patient's being classified as having only colon cancer Evidence of laparoscopically-assisted colectomy, unless patients are participating in the Intergroup Protocol INT 0146 or the Australasian, Multi-center, Prospective, Randomized, Clinical Study Comparing Laparoscopic and Conventional Open Surgical Treatments of Colon Cancer in Adults (ALCCaS) Isolated, distant, or noncontiguous intra-abdominal metastases, even if resected, will render the patient ineligible Clinically significant peripheral neuropathy at the time of randomization (defined in the NCI Common Toxicity Criteria [CTC] as grade 2 or greater neurosensory or neuromotor toxicity)

Sites / Locations

  • National Surgical Adjuvant Breast and Bowel Project

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I

Arm II

Arm Description

Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.

Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.

Outcomes

Primary Outcome Measures

DFS rate

Secondary Outcome Measures

Survival rate

Full Information

First Posted
March 7, 2000
Last Updated
January 10, 2013
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004931
Brief Title
Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
Official Title
A Clinical Trial Comparing 5-Fluorouracil (5-FU) Plus Leucovorin (LV) and Oxaliplatin With 5-FU Plus LV for the Treatment of Patients With Stages II and III Carcinoma of the Colon
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
February 2000 (undefined)
Primary Completion Date
September 2005 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief Summary
Randomized phase III trial to compare the effectiveness of fluorouracil plus leucovorin with or without oxaliplatin in treating patients who have stage II or stage III colon cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective for colon cancer
Detailed Description
PRIMARY OBJECTIVES: I. To compare the relative efficacy of 5-FU + LV + Oxaliplatin (FLOX) with that of 5-FU + LV (FL) in prolonging DFS. SECONDARY OBJECTIVES: I. To compare the relative efficacy of FLOX with FL in prolonging S. OUTLINE: This is a randomized study. Patients are randomized to one of two treatment arms. ARM I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks. ARM II: Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I. Treatment in both arms repeats every 8 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 6, 9, and 12 months; every 6 months for 4 years; and then annually thereafter.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage II Colon Cancer, Stage III Colon Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2472 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.
Arm Title
Arm II
Arm Type
Experimental
Arm Description
Patients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
Other Intervention Name(s)
CF, CFR, LV
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Other Intervention Name(s)
5-fluorouracil, 5-Fluracil, 5-FU
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
oxaliplatin
Other Intervention Name(s)
1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
DFS rate
Time Frame
Time to first documented evidence of colon cancer recurrence, second primary cancer, or death from any cause without prior evidence of colon cancer recurrence or second primary cancer, assessed up to 3 years
Secondary Outcome Measure Information:
Title
Survival rate
Time Frame
Time to death from any cause, assessed up to 5 years

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must consent to be in the study and must have signed and dated an IRB-approved consent form conforming to federal and institutional guidelines In the opinion of the investigator, patients must have a 10-year life expectancy, excluding their diagnosis of cancer The interval between curative resection and randomization must be no more than 42 days The distal extent of the tumor must be >= 12 cm from the anal verge on endoscopy Patients must have colonic adenocarcinoma that meets one of the criteria below: Stage II carcinoma (T3, 4; N0; M0) - The tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues (T3) or directly invades other organs or structures, and/or perforates visceral peritoneum (T4), excluding free perforation Stage III carcinoma (any T; N1, 2; M0) - The tumor has invaded to any depth, with involvement of regional lymph nodes AGCs >= 1500/mm^3 Platelets >= 100,000/mm^3 Bilirubin within or below the normal limits for the laboratory Alkaline phosphatase within or below the normal limits for the laboratory SGOT or SGPT within or below the normal limits for the laboratory Serum creatinine within or below the normal limits for the laboratory Patients with more than one synchronous primary colon tumor are eligible; for the purpose of this protocol, staging classification will be based on the stage of the more advanced primary tumor Patients are eligible if adjacent structures (e.g., bladder, small intestine, ovary, etc.) involved by direct extension of the primary tumor are removed en bloc and if, in the judgement of the surgeon and by confirmation on histological examination (i.e., margins of resection are not involved), the resection is deemed to be "curative" Patients must have an ECOG performance status of 0, 1, or 2 Patients with intestinal obstruction are eligible; preliminary or complementary colostomy does not preclude entry Patients with prior noncolorectal malignancies are eligible if they have been disease-free for >= 5 years; patients with squamous or basal cell carcinoma of the skin that has been effectively treated, carcinoma in situ of the cervix that has been treated by operation only, or lobular carcinoma in situ of the breast are eligible, even if these conditions were diagnosed within 5 years prior to randomization Exclusion Criteria: Prior invasive colon or rectal malignancy, regardless of disease-free interval Current or past malignant colon tumors other than carcinoma, i.e., sarcoma, lymphoma, carcinoid, etc., regardless of disease-free interval Tumors located < 12 cm from the anal verge on preoperative endoscopy Tumors that demonstrate free perforation as manifested by free air or free fluid in the abdomen; patients with walled-off perforation are eligible Pregnancy or lactation at the time of proposed randomization; (5-FU and oxaliplatin are both teratogenic and mutagenic and may cause fetal harm;) eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods Noncurative surgical resection or prior chemotherapy or radiotherapy for this malignancy, with the exception of a decompressing colostomy Nonmalignant systemic disease (cardiovascular, renal, hepatic, etc.) that would preclude the patient's receiving either chemotherapy treatment option; specifically excluded are patients with active ischemic heart disease (class III or class IV myocardial disease -- New York Heart Association) or a recent history of myocardial infarction (within 6 months), or current symptomatic arrhythmia Class III: Patients with cardiac disease resulting in marked limitation of physical activity; such patients are comfortable at rest; less-than-ordinary physical activity causes fatigue, palpitation, dyspnea, or anginal pain Class IV: Patients with cardiac disease resulting in inability to perform any physical activity without discomfort; symptoms of cardiac insufficiency or the anginal syndrome may be present even at rest Psychiatric or addictive disorders that would preclude obtaining informed consent Multiple primary tumors involving both the colon and the rectum that would preclude the patient's being classified as having only colon cancer Evidence of laparoscopically-assisted colectomy, unless patients are participating in the Intergroup Protocol INT 0146 or the Australasian, Multi-center, Prospective, Randomized, Clinical Study Comparing Laparoscopic and Conventional Open Surgical Treatments of Colon Cancer in Adults (ALCCaS) Isolated, distant, or noncontiguous intra-abdominal metastases, even if resected, will render the patient ineligible Clinically significant peripheral neuropathy at the time of randomization (defined in the NCI Common Toxicity Criteria [CTC] as grade 2 or greater neurosensory or neuromotor toxicity)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Kuebler
Organizational Affiliation
NSABP Foundation Inc
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Surgical Adjuvant Breast and Bowel Project
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212-5234
Country
United States

12. IPD Sharing Statement

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Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer

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