Chemotherapy and Radiation Therapy Before Surgery Followed by Capecitabine With or Without Oxaliplatin in Treating Patients With Locally Advanced Rectal Cancer
Condition: Colorectal Cancer
MeSH terms: Rectal Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as capecitabine and oxaliplatin, work in
      different ways to stop the growth of tumor cells, either by killing the cells or by stopping
      them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving
      radiation therapy that uses a 3-dimensional image of the tumor to help focus thin beams of
      radiation directly on the tumor may kill more tumor cells and have fewer side effects. Giving
      chemotherapy together with radiation therapy before surgery may make the tumor smaller and
      reduce the amount of normal tissue that needs to be removed. Giving chemotherapy after
      surgery may kill any tumor cells that remain after surgery. It is not yet known whether
      capecitabine is more effective with or without oxaliplatin in treating patients with rectal
      cancer.

      PURPOSE: This randomized phase III trial is studying giving chemotherapy together with
      radiation therapy before surgery followed by capecitabine with or without oxaliplatin to see
      how well it works in treating patients with locally advanced rectal cancer.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Investigate whether the addition of oxaliplatin to neoadjuvant chemoradiotherapy and
           adjuvant chemotherapy comprising capecitabine improves disease-free survival in patients
           with locally advanced rectal cancer.

      Secondary

        -  Compare the overall survival of patients with locally advanced rectal cancer treated
           with neoadjuvant chemoradiotherapy and adjuvant chemotherapy comprising capecitabine
           with versus without oxaliplatin.

        -  Determine the loco-regional failure and distant failure of patients treated with these
           regimens.

        -  Determine the pathological down-staging (ypT0-2N0) of patients treated with these
           regimens.

        -  Determine the pathological complete remission (yp T0N0) rate of patients treated with
           these regimens.

        -  Determine the tumor progression grade and histopathological R0 resection of patients
           treated with these regimens.

        -  Determine the sphincter preservation rate of patients treated with these regimens.

        -  Determine the perioperative complication rate of these regimens in these patients.

        -  Determine the toxicity of these regimens in these patients.

      OUTLINE: This is a multicenter study. Patients are stratified according to treating center,
      clinical T category (T1-3 vs T4), clinical nodal status (Nx vs NO vs N1-2), distance from the
      tumor to the anal verge (≤ 5 cm vs > 5 cm) and method of locoregional staging (EUS+MRI vs
      EUS+CTscan vs MRI alone). Patients are randomized to 1 of 2 treatment arms.

        -  Arm I (control):

             -  Neoadjuvant therapy: Patients receive oral capecitabine twice daily on days 1-35.
                Patients also undergo concurrent 3-dimensional conformal radiotherapy 5 days a week
                on days 1-33 followed by surgery. Patients may receive additional chemoradiotherapy
                on days 36-38.

             -  Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oral
                capecitabine twice daily on days 1-15. Treatment repeats every 3 weeks for 6
                courses in the absence of disease progression or unacceptable toxicity.

        -  Arm II (investigational):

             -  Neoadjuvant therapy: Patients receive oral capecitabine twice daily and undergo
                concurrent 3-dimensional conformal radiotherapy 5 days a week on days 1-33.
                Patients also receive oxaliplatin IV over 1 hour on days 1, 8, 15, 22, and 29 prior
                to radiotherapy followed by surgery. Patients may receive additional
                chemoradiotherapy on days 36-38.

             -  Adjuvant therapy: Beginning 4-8 weeks after surgery, patients receive oxaliplatin
                IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-15. Treatment
                repeats every 3 weeks for 6 courses in the absence of disease progression or
                unacceptable toxicity.

      After completion of study therapy, patients are followed every 3 months for 3 years, and then
      every 6 months for 2 years.
    

Intervention name(s): capecitabine; oxaliplatin
Intervention type(s): Drug; Drug
Intervention description(s): Given orally; Given IV
Intervention MeSH terms: Capecitabine; Oxaliplatin
Allocation: Randomized
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage II rectal cancer; stage III rectal cancer; adenocarcinoma of the rectum