Oxaliplatin, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Rectum - Full Text View

Sponsors and Collaborators:	Roswell Park Cancer Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00086931

Purpose

RATIONALE: Drugs used in chemotherapy, such as oxaliplatin and capecitabine, work in 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. Oxaliplatin and capecitabine may make tumor cells more sensitive to radiation therapy and may kill more tumor cells. Giving chemotherapy with radiation therapy before surgery may shrink the tumor so that it can be removed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of oxaliplatin and capecitabine when given together with radiation therapy and to see how well they work in treating patients who are undergoing surgery for locally advanced cancer of the rectum. NOTE: *The phase I portion of this trial closed 06/2005. The best dose of oxaliplatin and capecitabine has been determined.

Condition	Intervention	Phase
Colorectal Cancer	Drug: capecitabine Drug: oxaliplatin Procedure: conventional surgery Procedure: neoadjuvant therapy Procedure: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Capecitabine Oxaliplatin

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer

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

Primary Outcome Measures:

Complete pathological response rate at time of surgery [ Designated as safety issue: No ]

Secondary Outcome Measures:

Disease-free survival, safety, and overall survival at 5 years [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	September 2003

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of neoadjuvant oxaliplatin and capecitabine when combined with radiotherapy in patients with locally advanced adenocarcinoma of the rectum. (Phase I closed to accrual as of 06/2005.)
Determine the rate of complete pathological response in patients treated with this regimen.

Secondary

Determine the overall survival of patients treated with this regimen.
Determine the rate of local and overall failure in patients treated with this regimen.
Determine the utility of TS, TP, DPD, ERCC-1, and apoptosis to predict response in patients treated with this regimen.
Determine the rate of pathologic down-staging in patients treated with this regimen.
Determine the safety and toxicity of this regimen in these patients.
Determine the rate of sphincter-saving rectal surgery in patients treated with this regimen who had been deemed candidates for abdominoperineal resection at diagnosis.

OUTLINE: This is a multicenter, phase I (phase I closed to accrual as of 06/2005), dose-escalation study of oxaliplatin and capecitabine followed by a phase II study.

Phase I (closed to accrual as of 06/2005): Patients undergo radiotherapy once daily 5 days a week for 5.5 weeks and receive oral capecitabine twice daily on days radiotherapy is administered. Beginning on day 1 of radiotherapy, patients also receive oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.

Cohorts of 3-6 patients receive escalating doses of oxaliplatin and capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Phase II: Patients undergo radiotherapy and receive capecitabine and oxaliplatin as in phase I at the MTD.

All patients undergo curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy.

Patients are followed every 3 months for 3 years and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 31-40 patients (6-15 for phase I [phase I closed to accrual as of 06/2005] and 25 for phase II) will be accrued for this study within 2 years.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the rectum
- Tumor involving the distal 12 cm of the rectum (above the anal verge)
- Clinically staged by endoscopic ultrasound with one of the following criteria:
  - T3-T4 disease
  - Evidence of lymph node involvement, defined by the presence of ≥ 1 enlarged peri-rectal lymph node (≥ 1 cm in size)
No known distant metastases

PATIENT CHARACTERISTICS:

Age

18 to 75

Performance status

ECOG 0-1 OR
Karnofsky 70-100%

Life expectancy

More than 1 year

Hematopoietic

WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal

Renal

Creatinine normal OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Other

Able to receive oral medication
No other malignancy within the past 5 years except nonmelanoma skin cancer
No prior or concurrent significant neuropathy
No prior allergic reaction attributed to compounds of similar chemical or biological composition to study drugs
No ongoing or active infection
No other concurrent uncontrolled illness
No psychiatric illness or social situation that would preclude study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective double-method contraception during and for 3 months after study participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent granulocyte-stimulating factors

Chemotherapy

No prior chemotherapy

Endocrine therapy

Not specified

Radiotherapy

No prior pelvic radiotherapy

Surgery

Not specified

Other

No other concurrent investigational agents
No other concurrent anticancer agents or therapies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086931

Locations

United States, New York
Erie County Medical Center Corporation
Buffalo, New York, United States, 14215
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215

Sponsors and Collaborators

Roswell Park Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Marwan Fakih, MD

Roswell Park Cancer Institute

More Information

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

Publications of Results:

Fakih MG, Rajput A, Yang GY, et al.: A phase I and biological correlates study of capecitabine (CAP) + oxaliplatin (OX) + radiation therapy (RT) in locally advanced rectal cancer (LARC). [Abstract] J Clin Oncol 23 (Suppl 16): A-3633, 279s, 2005.

Study ID Numbers:	CDR0000371830, RPCI-I-10803, SANOFI-RPCI-I-10803
Study First Received:	July 8, 2004
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00086931
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Capecitabine
Digestive System Neoplasms
Rectal Neoplasms
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Intestinal Neoplasms

Rectal neoplasm
Oxaliplatin
Digestive System Diseases
Gastrointestinal Neoplasms
Adenocarcinoma
Rectal cancer
Colorectal Neoplasms

Additional relevant MeSH terms:

Antimetabolites
Neoplasms
Antimetabolites, Antineoplastic
Neoplasms by Site

Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009