Radiation Therapy and Fluorouracil With or Without Combination Chemotherapy Followed by Surgery in Treating Patients With Stage II or Stage III Rectal Cancer
NCT ID: NCT00335816
Last Updated: 2026-01-14
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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ACTIVE_NOT_RECRUITING
PHASE2
248 participants
INTERVENTIONAL
2008-08-31
2026-12-31
Brief Summary
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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.
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Detailed Description
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I. 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.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Group 1 (Closed to Enrollment)
All 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..
fluorouracil
Given IV
conventional surgery
Patients undergo surgery
radiation therapy
Patients undergo radiotherapy
laboratory biomarker analysis
Correlative studies
DNA analysis
Correlative studies
polymerase chain reaction
Correlative studies
immunohistochemistry staining method
Correlative studies
Group 2 (Closed to Enrollment)
All 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.
fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
conventional surgery
Patients undergo surgery
radiation therapy
Patients undergo radiotherapy
laboratory biomarker analysis
Correlative studies
DNA analysis
Correlative studies
polymerase chain reaction
Correlative studies
immunohistochemistry staining method
Correlative studies
Group 3 (chemotherapy, FOLFOX, conventional surgery)
All 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.
fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
conventional surgery
Patients undergo surgery
radiation therapy
Patients undergo radiotherapy
laboratory biomarker analysis
Correlative studies
DNA analysis
Correlative studies
polymerase chain reaction
Correlative studies
immunohistochemistry staining method
Correlative studies
Group 4 (chemotherapy, FOLFOX, conventional surgery)
All 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.
fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
conventional surgery
Patients undergo surgery
radiation therapy
Patients undergo radiotherapy
laboratory biomarker analysis
Correlative studies
DNA analysis
Correlative studies
polymerase chain reaction
Correlative studies
immunohistochemistry staining method
Correlative studies
Interventions
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fluorouracil
Given IV
leucovorin calcium
Given IV
oxaliplatin
Given IV
conventional surgery
Patients undergo surgery
radiation therapy
Patients undergo radiotherapy
laboratory biomarker analysis
Correlative studies
DNA analysis
Correlative studies
polymerase chain reaction
Correlative studies
immunohistochemistry staining method
Correlative studies
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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:
* 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
18 Years
ALL
No
Sponsors
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National Cancer Institute (NCI)
NIH
Memorial Sloan Kettering Cancer Center
OTHER
Responsible Party
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Principal Investigators
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Julio Garcia-Aguilar, MD, PhD
Role: STUDY_CHAIR
Memorial Sloan Kettering Cancer Center
Locations
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Cancer Care Center at John Muir Health - Concord Campus
Concord, California, United States
City of Hope Medical Center
Duarte, California, United States
St. Joseph Hospital Regional Cancer Center - Orange
Orange, California, United States
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Washington Cancer Institute at Washington Hospital Center
Washington D.C., District of Columbia, United States
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida
Tampa, Florida, United States
University of Chicago Cancer Research Center
Chicago, Illinois, United States
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
St Louis, Missouri, United States
Colon and Rectal Surgery, Incorporated
Omaha, Nebraska, United States
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States
Knight Cancer Institute at Oregon Health and Science University
Portland, Oregon, United States
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada
Countries
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References
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Related Links
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Memorial Sloan Kettering Cancer Center
Other Identifiers
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