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Colorectal CancerPhase 2NCT00335816

Radiation Therapy and Fluorouracil With or Without Combination Chemotherapy Followed by Surgery in Treating Patients With Stage II or Stage III Rectal Cancer

A Phase 2 study testing fluorouracil, leucovorin calcium and oxaliplatin in people with Colorectal Cancer, run by Memorial Sloan Kettering Cancer Center at 15 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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, leucovorin calcium and oxaliplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
248 participants
Where
15 sitesin 2 countries
Study dates
Aug 2008to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Patients must have an Eastern Cooperative Oncology Group (ECOG) Status of 0 or 1, or comparable Karnofsky performance status
  • Patients must have histologically confirmed invasive adenocarcinoma of the rectum Distal border of the tumor must be within 12 cm from the anal verge as measured on rigid proctoscopic exam
  • Patients must have Stage II (uT3-4, uN0) or Stage III (any T, uN1-2) tumors, as confirmed by ERUS or MRI; females with anterior tumors invading the posterior vaginal wall (uT4) and males with anterior tumors that invade the seminal vesicles or adjacent organs (uT4) will also be eligible provided they undergo an extended resection including the organs involved
  • Patients with high grade obstruction that impedes the ERUS exam are eligible for the study provided they can be staged by MRI
  • Patients with synchronous or metachronous colorectal cancer are eligible for the study on condition that they are treated for rectal cancer in accordance with the protocol
  • Patients with the following are NOT allowed on study:
Show all 30Show fewer
  • Metastatic disease or other primaries
  • Locally recurrent rectal cancer
  • Previously documented history of Familial Adenomatous Polyposis
  • History of Inflammatory Bowel Disease
  • History of prior radiation treatments to pelvis
  • History of clinically significant cardiac disease (i.e., Class 3-4 congestive heart failure, symptomatic coronary artery disease, uncontrolled arrhythmia, and/or myocardial infarction within the previous 6 months
  • History of uncontrolled seizures or clinically significant central nervous system disorders
  • History of psychiatric conditions or diminished capacity that could compromise the giving of informed consent, or interfere with study compliance
  • History of allergy and/or hypersensitivity to 5-fluorouracil (fluorouracil), leucovorin (leucovorin calcium), and/or oxaliplatin
  • History of difficulty or inability to take or absorb oral medications
  • Patients must have adequate bone marrow, hepatic and renal function within 7 days prior to registration
  • White blood cells (WBC) >= 3,000 mm^3
  • Absolute neutrophil count (ANC) > 1,500 mm^3
  • Hemoglobin > 9.5 mg/dl
  • Platelet count >= 100,000 mm^3
  • Total bilirubin =< 1.5 mg/dl
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.0 times institutional upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.0 times ULN
  • Alkaline phosphatase =< 2.0 times ULN
  • Serum creatinine =< 1.5 times ULN
  • Patients with hereditary non-polyposis colorectal cancer are eligible for the study provided they meet the rest of the eligibility criteria
  • Patients who have experienced a prior malignancy should have received potentially curative therapy for that malignancy, and should be cancer-free for at least five years from the date of initial diagnosis (Exceptions: patients treated for basal cell carcinoma, or carcinoma in-situ of the cervix)
  • Patients of reproductive potential should agree to use an effective method of birth control when undergoing treatments with known or possible mutagenic or teratogenic effects; all female participants of childbearing potential must have a negative urine or serum pregnancy test within two weeks prior to study registration
  • Patients or the patient's legally acceptable representative must provide written authorization to allow the use and disclosure of protected health information; NOTE: this may be obtained in either the study-specific informed consent or in a separate authorization form and must be obtained from the patient prior to study registration or the initiation of any study-specific procedures

Who cannot join

None listed.

Trial locations and contacts

15 sites in 2 countries.

15 sites in 2 countries

United States14 sites

  • Vermont Cancer Center at University of Vermont

    Burlington, Vermont, 05405-0110

  • University of Chicago Cancer Research Center

    Chicago, Illinois, 60637-1470

  • Cleveland Clinic Taussig Cancer Center

    Cleveland, Ohio, 44195

  • Cancer Care Center at John Muir Health - Concord Campus

    Concord, California, 94524-4110

  • City of Hope Medical Center

    Duarte, California, 91010-3000

  • Masonic Cancer Center at University of Minnesota

    Minneapolis, Minnesota, 55455

  • Colon and Rectal Surgery, Incorporated

    Omaha, Nebraska, 68114

  • St. Joseph Hospital Regional Cancer Center - Orange

    Orange, California, 92868-3849

  • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

    Orange, California, 92868

  • Knight Cancer Institute at Oregon Health and Science University

    Portland, Oregon, 97239-3098

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center and Research Institute at University of South Florida

    Tampa, Florida, 33612-9497

  • Washington Cancer Institute at Washington Hospital Center

    Washington D.C., District of Columbia, 20010

Other trials in United States

Canada1 site

  • Tom Baker Cancer Centre - Calgary

    Calgary, Alberta, T2N 4N2

Other trials in Canada

About this study

Official title: Timing of Rectal Cancer Response to Chemoradiation

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as fluorouracil, oxaliplatin, and leucovorin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Fluorouracil may also make tumor cells more sensitive to radiation therapy. Leucovorin calcium may protect normal cells from the side effects of chemotherapy, and it may help fluorouracil work better by making tumor cells more sensitive to the drug. Giving radiation therapy together with chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well giving radiation therapy together with fluorouracil with or without combination therapy works in treating patients who are undergoing surgery for stage II or stage III rectal cancer.

Read the detailed description

OBJECTIVES:

  1. To determine the rate of pathologic complete response to chemoradiation (no evidence of residual tumor in the resected specimen) of Stage II and Stage III rectal cancers that are staged preoperatively by endorectal ultrasound (ERUS) or magnetic resonance imaging (MRI), treated according to a standardized chemoradiation and surgery protocol, and evaluated by a systematic pathologic exam of the surgical specimen.

II. To study the effect of different chemoradiation-to-surgery intervals on the rate of pathologic complete response, on surgical difficulty, and on postoperative complications.

III. To investigate the feasibility of using sensitive molecular assays to detect tumor cells in the tumor bed and regional lymph nodes of rectal cancer specimens, with or without pathologic complete response to preoperative chemoradiation.

OUTLINE:

Patients are assigned to 1 of 4 treatment groups. All patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil intravenously (IV) continuously over 24 hours 7 days a week for 6 weeks.

GROUP I (closed to enrollment): Patients undergo standard surgical resection after completion of chemoradiation therapy.

GROUP II (closed to enrollment): Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2. Treatment repeats every 14 days for 2 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

GROUP III: Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 4 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.

GROUP IV: Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 6 courses. After the last week of post- radiation chemotherapy, patients undergo standard surgical resection.

In all groups, treatment continues in the absence of disease progression or unacceptable toxicity. A

fter completion of study treatment, patients are followed up for 5 years.

Keywords
stage II rectal cancer, stage III rectal cancer, adenocarcinoma of the rectum
Medical subject headings
Colorectal Neoplasms, Rectal Neoplasms

What participants receive

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

Study groups in NCT00335816
Study groupRoleWhat they receive
Group 1 (Closed to Enrollment)ExperimentalAll patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil intravenously continuously over 24 hours 7 days a week for 6 weeks. Patients undergo standard surgical resection after completion of chemoradiation therapy..
Receives: Drug: fluorouracil; Procedure: conventional surgery; Radiation: radiation therapy; Other: laboratory biomarker analysis; Genetic: DNA analysis; Genetic: polymerase chain reaction; Other: immunohistochemistry staining method
Group 2 (Closed to Enrollment)ExperimentalAll patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1-2. Treatment repeats every 14 days for 2 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.
Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: conventional surgery; Radiation: radiation therapy; Other: laboratory biomarker analysis; Genetic: DNA analysis; Genetic: polymerase chain reaction; Other: immunohistochemistry staining method
Group 3 (chemotherapy, FOLFOX, conventional surgery)ExperimentalAll patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 4 courses. After the last week of post-radiation chemotherapy, patients undergo standard surgical resection.
Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: conventional surgery; Radiation: radiation therapy; Other: laboratory biomarker analysis; Genetic: DNA analysis; Genetic: polymerase chain reaction; Other: immunohistochemistry staining method
Group 4 (chemotherapy, FOLFOX, conventional surgery)ExperimentalAll patients undergo chemoradiation therapy comprising radiation therapy once daily 5 days a week for 5 weeks and fluorouracil IV continuously over 24 hours 7 days a week for 6 weeks. Beginning 4 weeks after completion of chemoradiation therapy, patients receive modified FOLFOX-6 chemotherapy as in group II. Treatment repeats every 14 days for 6 courses. After the last week of post- radiation chemotherapy, patients undergo standard surgical resection. Patients then receive 3 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.
Receives: Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin; Procedure: conventional surgery; Radiation: radiation therapy; Other: laboratory biomarker analysis; Genetic: DNA analysis; Genetic: polymerase chain reaction; Other: immunohistochemistry staining method

What is being measured

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

  1. Rate of pathologic complete response

    Measured: Determined at the time of surgery

  2. Effect of different chemoradiation-to-surgery intervals on rate of pathologic complete response and surgical difficulty.

    Measured: Measured at the time of surgery

  3. Effect of different chemoradiation-to-surgery intervals on postoperative complications

    Measured: 30 days after surgery

Timeline

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

  1. First posted12 Jun 2006 (estimated)
  2. Study startAug 2008
  3. Primary completionDec 2026 (estimated)
  4. Study completionDec 2026 (estimated)

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
248 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00335816
Sponsor's protocol ID
mskcc 12-201
Other IDs
P30CA033572, R01CA090559, CDR0000458059
Status last verified
Jan 2026
First submitted
8 Jun 2006
Last updated
14 Jan 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • Pelossof R, Chow OS, Fairchild L, Smith JJ, Setty M, Chen CT, Chen Z, Egawa F, Avila K, Leslie CS, Garcia-Aguilar J. Integrated genomic profiling identifies microRNA-92a regulation of IQGAP2 in locally advanced rectal cancer. Genes Chromosomes Cancer. 2016 Apr;55(4):311-321. doi: 10.1002/gcc.22329.

    PubMed 26865277

  • Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, Kumar AS, Oommen S, Coutsoftides T, Hunt SR, Stamos MJ, Ternent CA, Herzig DO, Fichera A, Polite BN, Dietz DW, Patil S, Avila K; Timing of Rectal Cancer Response to Chemoradiation Consortium. Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial. Lancet Oncol. 2015 Aug;16(8):957-66. doi: 10.1016/S1470-2045(15)00004-2. Epub 2015 Jul 14.

    PubMed 26187751

  • Duldulao MP, Lee W, Nelson RA, Li W, Chen Z, Kim J, Garcia-Aguilar J. Mutations in specific codons of the KRAS oncogene are associated with variable resistance to neoadjuvant chemoradiation therapy in patients with rectal adenocarcinoma. Ann Surg Oncol. 2013 Jul;20(7):2166-71. doi: 10.1245/s10434-013-2910-0. Epub 2013 Mar 2.

    PubMed 23456389

  • Duldulao MP, Lee W, Streja L, Chu P, Li W, Chen Z, Kim J, Garcia-Aguilar J. Distribution of residual cancer cells in the bowel wall after neoadjuvant chemoradiation in patients with rectal cancer. Dis Colon Rectum. 2013 Feb;56(2):142-9. doi: 10.1097/DCR.0b013e31827541e2.

    PubMed 23303141

  • Duldulao MP, Lee W, Nelson RA, Ho J, Le M, Chen Z, Li W, Kim J, Garcia-Aguilar J. Gene polymorphisms predict toxicity to neoadjuvant therapy in patients with rectal cancer. Cancer. 2013 Mar 1;119(5):1106-12. doi: 10.1002/cncr.27862. Epub 2012 Oct 23.

    PubMed 23096768

  • Chen Z, Liu Z, Deng X, Warden C, Li W, Garcia-Aguilar J. Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer. Dis Colon Rectum. 2012 Jun;55(6):677-85. doi: 10.1097/DCR.0b013e31824f873f.

    PubMed 22595848

  • Duldulao MP, Lee W, Le M, Wiatrek R, Nelson RA, Chen Z, Li W, Kim J, Garcia-Aguilar J. Surgical complications and pathologic complete response after neoadjuvant chemoradiation in locally advanced rectal cancer. Am Surg. 2011 Oct;77(10):1281-5.

    PubMed 22127070

  • Garcia-Aguilar J, Chen Z, Smith DD, Li W, Madoff RD, Cataldo P, Marcet J, Pastor C. Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer. Ann Surg. 2011 Sep;254(3):486-92; discussion 492-3. doi: 10.1097/SLA.0b013e31822b8cfa.

    PubMed 21865946

  • Duldulao MP, Lee W, Le M, Chen Z, Li W, Wang J, Gao H, Li H, Kim J, Garcia-Aguilar J. Gene expression variations in microsatellite stable and unstable colon cancer cells. J Surg Res. 2012 May 1;174(1):1-6. doi: 10.1016/j.jss.2011.06.016. Epub 2011 Jul 7.

    PubMed 21816436

  • Chen Z, Liu Z, Li W, Qu K, Deng X, Varma MG, Fichera A, Pigazzi A, Garcia-Aguilar J. Chromosomal copy number alterations are associated with tumor response to chemoradiation in locally advanced rectal cancer. Genes Chromosomes Cancer. 2011 Sep;50(9):689-99. doi: 10.1002/gcc.20891. Epub 2011 May 16.

    PubMed 21584903

  • Garcia-Aguilar J, Smith DD, Avila K, Bergsland EK, Chu P, Krieg RM; Timing of Rectal Cancer Response to Chemoradiation Consortium. Optimal timing of surgery after chemoradiation for advanced rectal cancer: preliminary results of a multicenter, nonrandomized phase II prospective trial. Ann Surg. 2011 Jul;254(1):97-102. doi: 10.1097/SLA.0b013e3182196e1f.

    PubMed 21494121

  • Chen Z, Duldulao MP, Li W, Lee W, Kim J, Garcia-Aguilar J. Molecular diagnosis of response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer. J Am Coll Surg. 2011 Jun;212(6):1008-1017.e1. doi: 10.1016/j.jamcollsurg.2011.02.024. Epub 2011 Mar 31.

    PubMed 21458303

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing fluorouracil, leucovorin calcium and oxaliplatin in people with Colorectal Cancer, run by Memorial Sloan Kettering Cancer Center at 15 sites in 2 countries.

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 30 inclusion and 0 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: under way, not looking for participants, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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?

Rate of pathologic complete response (time frame: Determined at the time of surgery). The study lists 3 primary outcomes in all. 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 NCT00335816, which also lists 12 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 2026.

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