Oxaliplatin, Capecitabine, and Radiation Therapy in Treating Patients With Locally Advanced Cancer of the Rectum
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      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.
    

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.
    

Intervention name(s): capecitabine; oxaliplatin; conventional surgery; neoadjuvant therapy; radiation therapy
Intervention type(s): Drug; Drug; Procedure; Procedure; Radiation
Intervention description(s): oral dose escalating, twice daily.; IV over 2 hours on days 1, 8, 15, 22, and 29.; curative-intent surgery 6-8 weeks after the completion of chemoradiotherapy; chemotherapy and radiation prior to surgery; once daily 5 days a week for 5.5 weeks
Intervention MeSH terms: Capecitabine; Oxaliplatin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adenocarcinoma of the rectum; stage III rectal cancer; stage II rectal cancer