Chemotherapy, Radiation Therapy, and Surgery in Treating Patients With Rectal Cancer - Full Text View

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00003799

Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, radiation therapy, and surgery may be effective treatment for rectal cancer.

PURPOSE: Phase I trial to study the effectiveness of radiation therapy plus chemotherapy followed by surgery and additional chemotherapy in treating patients who have advanced nonmetastatic primary cancer of the rectum.

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

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	Phase I Study of Preoperative Radiation Therapy With Concurrent Protracted Continuous Infusion 5-FU and Dose Escalating Oxaliplatin Followed by Surgery, Adjuvant Oxaliplatin, 5-FU, and Leucovorin for Locally Advanced (T3 and T4) Rectal Adenocarcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

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

U.S. FDA Resources

Further study details as provided by Eastern Cooperative Oncology Group:

Estimated Enrollment:	20
Study Start Date:	May 1999
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose and dose-limiting toxicity of oxaliplatin when combined preoperatively with concurrent radiotherapy and fluorouracil in patients with locally advanced rectal adenocarcinoma.
Evaluate the resection rate for T4 rectal cancers, the pathological complete response rate for T3 and T4 rectal cancers, and the expected vs actual type of resection (abdominoperineal resection vs low anterior resection [LAR] vs LAR/coloanal anastomosis) in patients treated with this regimen.
Determine survival and patterns of recurrence in this patient population after this treatment regimen.
Evaluate anastomotic and sphincter function in these patients after preoperative combined modality therapy.

OUTLINE: This is a dose-escalation study of preoperative oxaliplatin.

Patients receive fluorouracil IV continuously with concurrent radiotherapy for 5.5 weeks. Patients also receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5.

Cohorts of 5 patients each receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 5 patients experience dose-limiting toxicity. Additional patients are treated at the MTD.

Patients undergo surgery 6-8 weeks after completing preoperative chemotherapy and radiotherapy. The surgical procedure is determined by the extent of the tumor before preoperative therapy. The type of operative procedure may be abdominoperineal resection, low anterior resection (LAR), or LAR/coloanal anastomosis.

Postoperative chemotherapy begins within 6 weeks after surgery, comprising leucovorin calcium and fluorouracil IV on days 1-5. Treatment repeats every 21 days for 4 courses.

Patients are followed every 3 months for 2.5 years, every 6 months for 3 years, then annually for 5 years.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study within 1 year.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed locally advanced, nonmetastatic primary adenocarcinoma of the rectum
- Stage II or III (T3 or T4)
- Clinically resectable OR
- Clinically fixed or initially not completely resectable (T4, N0-2, M0) based on the presence of at least one of the following criteria:
  - Clinically fixed tumor on rectal exam with tumor adherent to the pelvic sidewall or sacrum
  - Sciatica attributed to sacral root invasion with CT scan/MRI evidence of lack of clear tissue plane as evidence of fixation
  - Hydronephrosis on CT scan or IVP, or ureteric or bladder invasion by cystoscopy and cytology or biopsy, or invasion into prostate
  - Vaginal or uterine involvement
No tumor outside of the pelvis, including:
- Liver metastases
- Peritoneal seeding
- Metastatic inguinal lymphadenopathy
Distal border of tumor must be at or below the peritoneal reflection, defined as within 12 cm of anal verge by proctoscopic exam
Transmural penetration through the muscularis propria demonstrated by CT scan plus endorectal ultrasound or MRI
No high-grade (lumen diameter less than 1 cm) large bowel obstruction, unless diverting colostomy has been performed

PATIENT CHARACTERISTICS:

Age:

18 and over

Performance status:

ECOG 0-2

Life expectancy:

Not specified

Hematopoietic:

WBC at least 3500/mm^3
Platelet count at least 100,000/mm^3

Hepatic:

Bilirubin less than 2.0 mg/dL
Alkaline phosphatase no greater than 2 times upper limit of normal (ULN)
SGOT no greater than 2 times ULN

Renal:

Creatinine no greater than 2.0 mg/dL

Other:

Caloric intake at least 1500 kilocalories per day
No other prior malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix
No active inflammatory bowel disease
No other serious medical illness
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

Not specified

Chemotherapy:

No prior chemotherapy

Endocrine therapy:

Not specified

Radiotherapy:

No prior pelvic radiotherapy
No concurrent intraoperative radiotherapy or brachytherapy

Surgery:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003799

Locations

United States, Georgia
Emory University Hospital - Atlanta
Atlanta, Georgia, United States, 30322
Veterans Affairs Medical Center - Atlanta (Decatur)
Decatur, Georgia, United States, 30033
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:

David I. Rosenthal, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

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

Publications:

Rosenthal DI, Catalano PJ, Haller DG, Landry JC, Sigurdson ER, Spitz FR, Benson AB 3rd. Phase I Study of Preoperative Radiation Therapy With Concurrent Infusional 5-Fluorouracil and Oxaliplatin Followed by Surgery and Postoperative 5-Fluorouracil Plus Leucovorin for T3/T4 Rectal Adenocarcinoma: ECOG E1297. Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):108-13.

Rosenthal DI, Catalano P, Haller DG, et al.: ECOG 1297: A phase I study of preoperative radiaton therapy (RT) with concurrent protracted continuous infusion 5-FU and dose escalating oxaliplatin followed by surgery, adjuvant 5-FU, and leucovorin for locally advanced (T3/4) rectal adenocarcinoma. [Abstract] Proceedings of the American Society of Clinical Oncology 22: A-1094, 2003.

Ryan DP. Rectal cancer: integrating oxaliplatin into chemoradiation studies. Oncology (Huntingt). 2000 Dec;14(12 Suppl 11):38-41. Review.

ClinicalTrials.gov Identifier:	NCT00003799 History of Changes
Other Study ID Numbers:	CDR0000066943, U10CA021115, ECOG-1297
Study First Received:	November 1, 1999
Last Updated:	November 12, 2010
Health Authority:	United States: Federal Government

Keywords provided by Eastern Cooperative Oncology Group:

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

Additional relevant MeSH terms:

Adenocarcinoma
Rectal Neoplasms
Colorectal Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases

Colonic Diseases
Adjuvants, Immunologic
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 12, 2012