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Stage II Colon CancerPhase 3NCT00004931

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

A Phase 3 study testing leucovorin calcium, fluorouracil and oxaliplatin in people with Stage II Colon Cancer and Stage III Colon Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Any age
Conditions the study is for
Stage II Colon Cancer, Stage III Colon Cancer
What is being tested?
leucovorin calcium, fluorouracil and oxaliplatin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2,472 participants
Where
1 siteUnited States
Study dates
Feb 2000to Sep 2005
Phase
Phase 3
Are there results?
None posted in the registry

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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Surgical Adjuvant Breast and Bowel Project

    Pittsburgh, Pennsylvania, 15212-5234

Other trials in United States

About this study

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

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

Read the detailed description

PRIMARY OBJECTIVES:

  1. To compare the relative efficacy of 5-FU + LV + Oxaliplatin (FLOX) with that of 5-FU + LV (FL) in prolonging DFS.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
leucovorin calcium, fluorouracil, oxaliplatin, laboratory biomarker analysis
Medical subject headings
Colonic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • leucovorin calciumDrug

    Also called CF, CFR, LV

    Given IV

  • fluorouracilDrug

    Also called 5-fluorouracil, 5-Fluracil, 5-FU

    Given IV

  • oxaliplatinDrug

    Also called 1-OHP, Dacotin, Dacplat, Eloxatin

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT00004931
Study groupRoleWhat they receive
Arm IExperimentalPatients receive leucovorin calcium IV over 2 hours and fluorouracil IV (administered after 1 hour of leucovorin calcium) weekly for 6 weeks.
Receives: Drug: leucovorin calcium; Drug: fluorouracil; Other: laboratory biomarker analysis
Arm IIExperimentalPatients receive oxaliplatin IV over 2 hours on days 1, 15, and 29 and leucovorin calcium and fluorouracil as in arm I.
Receives: Drug: leucovorin calcium; Drug: fluorouracil; Drug: oxaliplatin; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. DFS rate

    Measured: 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 outcomes (1)

  1. Survival rate

    Measured: Time to death from any cause, assessed up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 May 2003 (estimated)
  2. Study startFeb 2000
  3. Primary completionSep 2005

Resources

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
2,472 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00004931
Sponsor's protocol ID
NCI-2012-03165
Other IDs
NSABP-C-07, U10CA012027
Status last verified
Jan 2013
First submitted
7 Mar 2000
Last updated
14 Jan 2013
Results posted
No

Publications

  • Chen L, Wang Y, Cai C, Ding Y, Kim RS, Lipchik C, Gavin PG, Yothers G, Allegra CJ, Petrelli NJ, Suga JM, Hopkins JO, Saito NG, Evans T, Jujjavarapu S, Wolmark N, Lucas PC, Paik S, Sun M, Pogue-Geile KL, Lu X. Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer. J Clin Oncol. 2024 May 1;42(13):1520-1530. doi: 10.1200/JCO.23.01080. Epub 2024 Feb 5.

    PubMed 38315963

  • Cohen R, Taieb J, Fiskum J, Yothers G, Goldberg R, Yoshino T, Alberts S, Allegra C, de Gramont A, Seitz JF, O'Connell M, Haller D, Wolmark N, Erlichman C, Zaniboni A, Lonardi S, Kerr R, Grothey A, Sinicrope FA, Andre T, Shi Q. Microsatellite Instability in Patients With Stage III Colon Cancer Receiving Fluoropyrimidine With or Without Oxaliplatin: An ACCENT Pooled Analysis of 12 Adjuvant Trials. J Clin Oncol. 2021 Feb 20;39(6):642-651. doi: 10.1200/JCO.20.01600. Epub 2020 Dec 23.

    PubMed 33356421

  • Salem ME, Yin J, Goldberg RM, Pederson LD, Wolmark N, Alberts SR, Taieb J, Marshall JL, Lonardi S, Yoshino T, Kerr RS, Yothers G, Grothey A, Andre T, De Gramont A, Shi Q. Evaluation of the change of outcomes over a 10-year period in patients with stage III colon cancer: pooled analysis of 6501 patients treated with fluorouracil, leucovorin, and oxaliplatin in the ACCENT database. Ann Oncol. 2020 Apr;31(4):480-486. doi: 10.1016/j.annonc.2019.12.007. Epub 2020 Jan 16.

    PubMed 32085892

  • Taieb J, Shi Q, Pederson L, Alberts S, Wolmark N, Van Cutsem E, de Gramont A, Kerr R, Grothey A, Lonardi S, Yoshino T, Yothers G, Sinicrope FA, Zaanan A, Andre T. Prognosis of microsatellite instability and/or mismatch repair deficiency stage III colon cancer patients after disease recurrence following adjuvant treatment: results of an ACCENT pooled analysis of seven studies. Ann Oncol. 2019 Sep 1;30(9):1466-1471. doi: 10.1093/annonc/mdz208.

    PubMed 31268130

  • Song N, Pogue-Geile KL, Gavin PG, Yothers G, Kim SR, Johnson NL, Lipchik C, Allegra CJ, Petrelli NJ, O'Connell MJ, Wolmark N, Paik S. Clinical Outcome From Oxaliplatin Treatment in Stage II/III Colon Cancer According to Intrinsic Subtypes: Secondary Analysis of NSABP C-07/NRG Oncology Randomized Clinical Trial. JAMA Oncol. 2016 Sep 1;2(9):1162-9. doi: 10.1001/jamaoncol.2016.2314.

    PubMed 27270348

  • Yothers G, O'Connell MJ, Lee M, Lopatin M, Clark-Langone KM, Millward C, Paik S, Sharif S, Shak S, Wolmark N. Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. J Clin Oncol. 2013 Dec 20;31(36):4512-9. doi: 10.1200/JCO.2012.47.3116. Epub 2013 Nov 12.

    PubMed 24220557

  • Yothers G, Sargent DJ, Wolmark N, Goldberg RM, O'Connell MJ, Benedetti JK, Saltz LB, Dignam JJ, Blackstock AW; ACCENT Collaborative Group. Outcomes among black patients with stage II and III colon cancer receiving chemotherapy: an analysis of ACCENT adjuvant trials. J Natl Cancer Inst. 2011 Oct 19;103(20):1498-506. doi: 10.1093/jnci/djr310. Epub 2011 Oct 12.

    PubMed 21997132

  • Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. doi: 10.1200/JCO.2011.36.4539. Epub 2011 Aug 22.

    PubMed 21859995

  • Fumagalli D, Gavin PG, Taniyama Y, Kim SI, Choi HJ, Paik S, Pogue-Geile KL. A rapid, sensitive, reproducible and cost-effective method for mutation profiling of colon cancer and metastatic lymph nodes. BMC Cancer. 2010 Mar 16;10:101. doi: 10.1186/1471-2407-10-101.

    PubMed 20233444

  • Kuebler JP, Colangelo L, O'Connell MJ, Smith RE, Yothers G, Begovic M, Robinson B, Seay TE, Wolmark N. Severe enteropathy among patients with stage II/III colon cancer treated on a randomized trial of bolus 5-fluorouracil/leucovorin plus or minus oxaliplatin: a prospective analysis. Cancer. 2007 Nov 1;110(9):1945-50. doi: 10.1002/cncr.23013.

    PubMed 17853393

  • Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. doi: 10.1200/JCO.2006.08.2974. Epub 2007 Apr 30.

    PubMed 17470851

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing leucovorin calcium, fluorouracil and oxaliplatin in people with Stage II Colon Cancer and Stage III Colon Cancer, run by National Cancer Institute (NCI) 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 14 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: finished, as of the sponsor's last update on 14 Jan 2013. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

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). 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 NCT00004931, which also lists 11 linked publications.

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 14 Jan 2013.

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