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

Sponsor:	City of Hope Medical Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	City of Hope Medical Center
ClinicalTrials.gov Identifier:	NCT00335816

Purpose

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. 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.

Condition	Intervention	Phase
Colorectal Cancer	Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: conventional surgery Radiation: radiation therapy	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Timing of Rectal Cancer Response to Chemoradiation

Resource links provided by NLM:

MedlinePlus related topics: Calcium Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Oxaliplatin Calcium gluconate Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:

Rate of pathologic complete response [ Time Frame: Determined at the time of surgery ] [ Designated as safety issue: No ]
Effect of different chemoradiation-to-surgery intervals on rate of pathologic complete response and surgical difficulty. [ Time Frame: Measured at the time of surgery ] [ Designated as safety issue: No ]
Effect of different chemoradiation-to-surgery intervals on postoperative complications [ Time Frame: 30 days after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment:	248
Study Start Date:	August 2008
Estimated Primary Completion Date:	December 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group 1 Patients undergo chemoradiotherapy comprising radiotherapy once daily 5 days a week for 5 weeks and fluorouracil (5-FU) IV continuously over 24 hours 7 days a week for 5 weeks (weeks 1-5). Patients undergo surgical resection of the rectum in week 12. Patients then receive 9 courses of FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU or other chemotherapy off study as directed by the physician.	Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy
Experimental: Group 2 Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed by bolus 5-FU on day 1 and 5-FU IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 2 courses. Patients undergo surgical resection of the rectum in week 16. Patients then receive 7 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.	Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy
Experimental: Group 3 Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU as in group 2. Treatment repeats every 14 days for 4 courses. Patients undergo surgical resection of the rectum in week 20. Patients then receive 5 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.	Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy
Experimental: Group 4 Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU as in group 2. Treatment repeats every 14 days for 6 courses. Patients undergo surgical resection of the rectum in week 24. Patients then receive 3 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.	Drug: fluorouracil Given IV Drug: leucovorin calcium Given IV Drug: oxaliplatin Given IV Procedure: conventional surgery Patients undergo surgery Radiation: radiation therapy Patients undergo radiotherapy

Detailed Description:

OBJECTIVES:

Determine the rate of pathologic complete response (i.e., no evidence of residual tumor in the resected specimen) in patients with stage II or III rectal cancer treated with neoadjuvant chemoradiotherapy comprising radiotherapy and fluorouracil with or without combination chemotherapy comprising oxaliplatin, leucovorin calcium, and fluorouracil followed by surgical resection.
Determine the effect of different chemoradiation-to-surgery intervals on the rate of pathologic complete response, surgical difficulty, and postoperative complications in these patients.

OUTLINE: This is a multicenter study. Patients are assigned to 1 of 4 treatment groups according to time of study enrollment.

Group 1: Patients undergo chemoradiotherapy comprising radiotherapy once daily 5 days a week for 5 weeks and fluorouracil (5-FU) IV continuously over 24 hours 7 days a week for 5 weeks (weeks 1-5). Patients undergo surgical resection of the rectum in week 12. Patients then receive 9 courses of FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU or other chemotherapy off study as directed by the physician.
Group 2: Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours followed by bolus 5-FU on day 1 and 5-FU IV continuously over 46 hours on days 1 and 2. Treatment repeats every 14 days for 2 courses. Patients undergo surgical resection of the rectum in week 16. Patients then receive 7 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.
Group 3: Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU as in group 2. Treatment repeats every 14 days for 4 courses. Patients undergo surgical resection of the rectum in week 20. Patients then receive 5 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.
Group 4: Patients undergo chemoradiotherapy as in group 1. Beginning in week 10, patients receive FOLFOX-6 chemotherapy comprising oxaliplatin, leucovorin calcium, and 5-FU as in group 2. Treatment repeats every 14 days for 6 courses. Patients undergo surgical resection of the rectum in week 24. Patients then receive 3 additional courses of FOLFOX-6 chemotherapy or other chemotherapy off study as directed by the physician.

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

After completion of study treatment, patients are followed for 1 month.

PROJECTED ACCRUAL: A total of 248 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

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
- Stage II (T3, N0) or Stage III (any T, N1) disease confirmed by endorectal ultrasound (ERUS) or MRI
  - Patients with a high-grade obstruction that impedes the ERUS exam are eligible if staged by MRI
Patients with synchronous or metachronous colorectal cancer are eligible provided they are treated for rectal cancer in accordance with this protocol
Hereditary non-polyposis colorectal cancer allowed provided the patient meets all study eligibility criteria
No metastatic disease or other primaries
No locally recurrent rectal cancer
No history of familial adenomatous polyposis

PATIENT CHARACTERISTICS:

Karnofsky performance status 60-100%
No history of any of the following significant cardiac diseases:
- New York Heart Association class III-IV congestive heart failure
- Symptomatic coronary artery disease
- Uncontrolled arrhythmia
- Myocardial infarction within the past 6 months
No history of inflammatory bowel disease
No history of uncontrolled seizures or clinically significant CNS disorders
No history of psychiatric conditions or diminished capacity that would preclude giving informed consent or complying with the study
No allergy and/or hypersensitivity to fluorouracil, leucovorin calcium, and/or oxaliplatin
No history of difficulty or inability to take or absorb oral medications
WBC ≥ 3,000/mm^3
Absolute neutrophil count > 1,500/mm^3
Hemoglobin > 9.5 g/dL
Platelet count ≥ 100,000/mm^3
Bilirubin ≤ 3mg/dL
AST and ALT ≤ 2.0 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.0 times ULN
Creatinine ≤ 1.5 times ULN
No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
Not pregnant
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

No prior radiotherapy to the pelvis
No other concurrent investigational drugs
No other concurrent anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00335816

Locations

United States, California
Cancer Care Center at John Muir Health - Concord Campus	Recruiting
Concord, California, United States, 94524-4110
Contact: Clinical Trials Office - Cancer Care Center at John Muir Healt 925-674-2580
City of Hope Comprehensive Cancer Center	Recruiting
Duarte, California, United States, 91010-3000
Contact: Clinical Trials Office - City of Hope Comprehensive Cancer Cen 800-826-4673 becomingapatient@coh.org
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center	Recruiting
Orange, California, United States, 92868
Contact: Clinical Trials Office - Chao Family Comprehensive Cancer Cent 877-827-8839 ucstudy@uci.edu
St. Joseph Hospital Regional Cancer Center - Orange	Recruiting
Orange, California, United States, 92868-3849
Contact: Theodore Coutsoftides, MD 714-532-2544
UCSF Helen Diller Family Comprehensive Cancer Center	Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office - UCSF Helen Diller Family Comprehensi 877-827-3222
United States, District of Columbia
Washington Cancer Institute at Washington Hospital Center	Recruiting
Washington, District of Columbia, United States, 20010
Contact: Clinical Trials Office - Washington Cancer Institute 202-877-8839
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute at University of South Florida	Recruiting
Tampa, Florida, United States, 33612-9497
Contact: Clinical Trials Office - H. Lee Moffitt Cancer Center and Rese 800-456-7121 canceranswers@moffitt.org
United States, Illinois
University of Chicago Cancer Research Center	Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Clinical Trials Office - University of Chicago Cancer Research 773-834-7424
United States, Minnesota
Masonic Cancer Center at University of Minnesota	Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office - Masonic Cancer Center at University o 612-624-2620
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Stephen Hunt, MD 314-454-7204
United States, Nebraska
Colon and Rectal Surgery, Incorporated	Recruiting
Omaha, Nebraska, United States, 68114
Contact: Charles A. Ternent, MD 402-343-1122
United States, Ohio
Cleveland Clinic Taussig Cancer Center	Recruiting
Cleveland, Ohio, United States, 44195
Contact: Clinical Trials Office - Cleveland Clinic Taussig Cancer Cente 866-223-8100
United States, Oregon
Knight Cancer Institute at Oregon Health and Science University	Recruiting
Portland, Oregon, United States, 97239-3098
Contact: Clinical Trials Office - Knight Cancer Institute at Oregon Hea 503-494-1080 trials@ohsu.edu
United States, Vermont
Vermont Cancer Center at University of Vermont	Recruiting
Burlington, Vermont, United States, 05405-0110
Contact: Clinical Trials Office - Vermont Cancer Center at University o 802-656-2178
Canada, Alberta
Tom Baker Cancer Centre - Calgary	Suspended
Calgary, Alberta, Canada, T2N 4N2

Sponsors and Collaborators

City of Hope Medical Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Julio Garcia-Aguilar, MD, PhD

Beckman Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided by City of Hope Medical Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Epub 2011 May 16.

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.

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. Epub 2011 Mar 31.

Responsible Party:	Julio Garcia-Aguilar, City of Hope Comprehensive Cancer Center
ClinicalTrials.gov Identifier:	NCT00335816 History of Changes
Other Study ID Numbers:	07182, P30CA033572, CHNMC-07182, UCSF-H44287-23127-03, UMN-2003UC036, UCSF-03451, CDR0000458059
Study First Received:	June 8, 2006
Last Updated:	August 10, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by City of Hope Medical Center:

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

Additional relevant MeSH terms:

Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Colonic Diseases
Fluorouracil
Oxaliplatin
Leucovorin

Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on February 09, 2012