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

NCT00335816 | Active Not Recruiting Phase 2 DMC

• 4 other identifiers: mskcc 12-201P30CA033572R01CA090559CDR0000458059
• Study Type: interventional
• Target: 248
• Locations: 2 countries
• Sites: 15

Brief 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. 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.

Conditions

Colorectal Cancer

Keywords

stage II rectal cancer; stage III rectal cancer; adenocarcinoma of the rectum

Outcome Measures

Primary Outcomes (3)

• Rate of pathologic complete response

  Determined at the time of surgery

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

  Measured at the time of surgery

• Effect of different chemoradiation-to-surgery intervals on postoperative complications

  30 days after surgery

Study Arms (4)

Group 1 (Closed to Enrollment)

EXPERIMENTAL

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..

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)

EXPERIMENTAL

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.

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)

EXPERIMENTAL

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.

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)

EXPERIMENTAL

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.

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

Interventions

radiation therapy RADIATION

Patients undergo radiotherapy

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

laboratory biomarker analysis OTHER

Correlative studies

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

DNA analysis GENETIC

Correlative studies

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

immunohistochemistry staining method OTHER

Correlative studies

Also known as: immunohistochemistry

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

polymerase chain reaction GENETIC

Correlative studies

Also known as: PCR

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

fluorouracil DRUG

Given IV

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

leucovorin calcium DRUG

Given IV

Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

oxaliplatin DRUG

Given IV

Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

conventional surgery PROCEDURE

Patients undergo surgery

Group 1 (Closed to Enrollment); Group 2 (Closed to Enrollment); Group 3 (chemotherapy, FOLFOX, conventional surgery); Group 4 (chemotherapy, FOLFOX, conventional surgery)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (15)

Cancer Care Center at John Muir Health - Concord Campus

Concord, California, 94524-4110, United States

Location

City of Hope Medical Center

Duarte, California, 91010-3000, United States

Location

St. Joseph Hospital Regional Cancer Center - Orange

Orange, California, 92868-3849, United States

Location

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

Orange, California, 92868, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Washington Cancer Institute at Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

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

Tampa, Florida, 33612-9497, United States

Location

University of Chicago Cancer Research Center

Chicago, Illinois, 60637-1470, United States

Location

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, 63110, United States

Location

Colon and Rectal Surgery, Incorporated

Omaha, Nebraska, 68114, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Knight Cancer Institute at Oregon Health and Science University

Portland, Oregon, 97239-3098, United States

Location

Vermont Cancer Center at University of Vermont

Burlington, Vermont, 05405-0110, United States

Location

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Related Publications (12)

• 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.

  PMID: 26865277 DERIVED

• 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.

  PMID: 26187751 DERIVED

• 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.

  PMID: 23456389 DERIVED

• 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.

  PMID: 23303141 DERIVED

• 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.

  PMID: 23096768 DERIVED

• 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.

  PMID: 22595848 DERIVED

• 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.

  PMID: 22127070 DERIVED

• 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.

  PMID: 21865946 DERIVED

• 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.

  PMID: 21816436 DERIVED

• 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.

  PMID: 21584903 DERIVED

• 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.

  PMID: 21494121 DERIVED

• 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.

  PMID: 21458303 DERIVED

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Colorectal Neoplasms; Rectal Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin; Radiotherapy; Polymerase Chain Reaction; Immunohistochemistry

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals; Therapeutics; Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Immunologic Techniques

Study Officials

• Julio Garcia-Aguilar, MD, PhD

  Memorial Sloan Kettering Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2006
• First Posted: June 12, 2006
• Study Start: August 1, 2008
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (14); CA (1)