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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT00086931
First received: July 8, 2004
Last updated: March 7, 2013
Last verified: March 2013
  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
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • Complete pathological response rate at time of surgery [ Time Frame: Time of surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease-free survival, safety, and overall survival at 5 years [ Time Frame: Continuous ] [ Designated as safety issue: Yes ]

Enrollment: 37
Study Start Date: September 2003
Study Completion Date: May 2010
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: capecitabine
    oral dose escalating, twice daily.
    Drug: oxaliplatin
    IV over 2 hours on days 1, 8, 15, 22, and 29.
    Procedure: conventional surgery
    curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy
    Procedure: neoadjuvant therapy
    chemotherapy and radiation prior to surgery
    Radiation: radiation therapy
    once daily 5 days a week for 5.5 weeks
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Sponsors and Collaborators
Roswell Park Cancer Institute
Investigators
Study Chair: Marwan Fakih, MD Roswell Park Cancer Institute
  More Information

Additional Information:
Publications:
Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT00086931     History of Changes
Other Study ID Numbers: I 10803, RPCI-I-10803, SANOFI-RPCI-I-10803
Study First Received: July 8, 2004
Last Updated: March 7, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roswell Park Cancer Institute:
adenocarcinoma of the rectum
stage III rectal cancer
stage II rectal cancer

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
Oxaliplatin
Capecitabine
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014