Combination Chemotherapy in Treating Patients Undergoing Surgery for Rectal Cancer - Full Text View

Sponsored by:	Beth Israel Medical Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00831181

Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) before surgery may kill more tumor cells and may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving oxaliplatin, leucovorin, and fluorouracil after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying the side effects and how well giving combination chemotherapy works in treating patients undergoing surgery for rectal cancer.

Condition	Intervention	Phase
Colorectal Cancer	Drug: FOLFOX regimen Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin Procedure: adjuvant therapy Procedure: neoadjuvant therapy Procedure: quality-of-life assessment Procedure: therapeutic surgical procedure	Phase II

MedlinePlus related topics: Cancer Colorectal Cancer Surgery

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase II Open- Labeled, Prospective Study to Determine the Efficacy of Pre- Operative Chemotherapy With Six Cycles of Modified FOLFOX 6 Followed by Total Mesorectal Excision (TME) Followed by an Additional Six Cycles of FOLFOX 6

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathologic response and complete response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Locoregional control [ Designated as safety issue: No ]
Complete resectability rates [ Designated as safety issue: No ]
Ability of high resolution pelvic MRI to assess locoregional response and predict adequacy of the circumferential margin after total mesorectal excision (TME) [ Designated as safety issue: No ]
Sphincter preservation [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Preservation of sexual, urinary, and bowel function [ Designated as safety issue: No ]
Patterns of disease failure, including local recurrence and distant metastasis assessed by CT scan [ Designated as safety issue: No ]
Quality of life at baseline and annually following TME [ Designated as safety issue: No ]
Comparison of preoperative stage with post-treatment pathologic stage [ Designated as safety issue: No ]
Comparison of preoperative staging with pelvic MRI vs endorectal ultrasound [ Designated as safety issue: No ]

Estimated Enrollment:	22
Study Start Date:	January 2009
Estimated Primary Completion Date:	January 2012 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To assess the complete pathologic response rate in patients with rectal cancer treated with modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.

Secondary

To observe the overall pathologic response rate in these patients.
To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
To assess toxic side effects of these regimens in these patients.
To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.

OUTLINE:

Neoadjuvant therapy: Patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then proceed to surgery.
Surgery: Patients undergo total mesorectal excision by anterior resection or an abdominal perineal resection within 4 weeks after completion of neoadjuvant therapy.
Adjuvant therapy: Within 4 weeks after surgery, patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients complete quality of life assessment questionnaires at baseline and at each follow-up visit.

After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
- T3, N0, M0 or T1-3, N1, M0 disease as assessed by clinical exam, transrectal ultrasound, MRI, and CT scan
  - No preoperative evidence of T4, N2 or distal lesions (0-6 cm from anal verge)
- Distal border of the tumor must be ≥ 6 cm from the anal verge on preoperative proctoscopy with the patient in the left lateral decubitus position
- Proximal border of the tumor must be ≤ 12 cm of the anal verge by proctoscopic examination
No known or distant metastases
No positive circumferential margin

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 60-100% or ECOG PS 0-1
ANC ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
Total bilirubin ≤ 1.5 times ULN
ALT ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situations that would limit compliance with study requirements
No serious comorbid disease, including psychiatric disorders and cardiopulmonary disease which precludes full delivery of study treatment
No other cancer diagnosis within the past 5 years, except nonmelanomatous skin cancers or in situ carcinoma of the cervix
No history of clinically significant peripheral neuropathy or current symptoms of neuropathy, defined as ≥ grade 2 neurosensory or neuromotor toxicity
No history of allergic reactions attributed to compounds of similar chemical or biological composition to fluorouracil, oxaliplatin, or leucovorin calcium
No HIV positivity

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or pelvic irradiation
No other concurrent investigational agents
No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
No concurrent halogenated antiviral agents (e.g., sorivudine or brivudine)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00831181

Locations

United States, New York
Beth Israel Medical Center - Philipps Ambulatory Care Center	Recruiting
New York, New York, United States, 10003
Contact: Clinical Trials Office - Beth Israel Medical Center - Philipps 212-844-8060
St. Luke's-Roosevelt Hospital Center - Roosevelt Division	Recruiting
New York, New York, United States, 10019
Contact: Tahir Mirzoyev 212-523-7289

Sponsors and Collaborators

Beth Israel Medical Center

Investigators

Principal Investigator:

Peter Kozuch, MD

Beth Israel Medical Center

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

Responsible Party:	Beth Israel Medical Center - Philipps Ambulatory Care Center ( Peter Kozuch )
Study ID Numbers:	CDR0000633360, BIMCP-OX-08-006, AVENTIS-BIMCP-OX-08-006
Study First Received:	January 27, 2009
Last Updated:	April 18, 2009
ClinicalTrials.gov Identifier:	NCT00831181 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Leucovorin
Rectal Diseases
Oxaliplatin
Vitamins
Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Rectal Neoplasm

Adjuvants, Immunologic
Trace Elements
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Calcium, Dietary
Rectal Cancer
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Adenocarcinoma
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Antineoplastic Agents
Colonic Diseases
Physiological Effects of Drugs
Leucovorin
Rectal Diseases
Oxaliplatin
Neoplasms by Site
Vitamins

Therapeutic Uses
Micronutrients
Digestive System Neoplasms
Vitamin B Complex
Growth Substances
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Pharmacologic Actions
Neoplasms
Digestive System Diseases
Fluorouracil
Gastrointestinal Neoplasms
Colorectal Neoplasms

ClinicalTrials.gov processed this record on May 06, 2009