Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

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.

Further Study Information

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.

Eligibility Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the rectum

• Tumor ≤ 12 cm from the anal verge

• Stage T3-4 or any node-positive disease

• No evidence of metastatic disease (confirmed by negative CT scan of the chest and abdomen)

• Resectable disease or expected to become resectable after preoperative chemoradiation

• May only be randomized once in this trial

PATIENT CHARACTERISTICS:

• WHO/ECOG performance status 0-2

• Hemoglobin ≥ 10.0 g/dL (transfusion allowed to achieve or maintain levels)

• ANC ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• ALT and AST ≤ 2.5 times upper level of normal (ULN)

• Alkaline phosphatase ≤ 2.5 times ULN

• Total bilirubin ≤ 1.5 times ULN

• Creatinine clearance > 50 mL/min

• Creatinine ≤ 1.5 times ULN

• Able to swallow tablets

• No prior or concurrent malignancies within the past 5 years except for adequately treated cone-biopsied carcinoma in situ of the cervix or basal cell carcinoma of the skin

• No clinically significant (i.e., active) cardiac disease, including any of the following:

• Congestive heart failure

• Symptomatic coronary artery disease

• Cardiac arrhythmia

• No myocardial infarction within the past 12 months

• No known significant impairment of intestinal resorption (e.g., chronic diarrhea, inflammatory bowel disease)

• No pre-existing conditions that would preclude chemoradiotherapy or radiotherapy (i.e., fistulas, severe ulcerative colitis [particularly patients currently taking sulfasalazine], Crohn's disease, or prior adhesions)

• No peripheral neuropathy ≥ grade 2 by CTCAE v3.0

• No serious uncontrolled intercurrent infections or other serious uncontrolled concomitant disease

• No history of uncontrolled seizures, central nervous system disorders or psychiatric disability that, in the opinion of the principal investigator, is clinically significant and would preclude giving informed consent or interfere with compliance with oral drug administration

• No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

• Not pregnant or nursing

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior cytotoxic chemotherapy or radiation therapy for rectal cancer

• No prior radiation therapy to the pelvis

• No prior or concurrent investigational drug, agent, or procedure

• More than 4 weeks since prior participation in the active or follow-up period of another investigational protocol

• No known allergy or any other adverse reaction to any of the study drugs or to any related compound

• No known dihydropyrimidine dehydrogenase deficiency

• No organ allograft requiring immunosuppressive therapy

• No concurrent sorivudine or chemically related analogues (e.g., brivudine)

Trial Contact Information

Trial Lead Organizations/Sponsors

European Organization for Research and Treatment of Cancer

Hans-Joachim Schmoll

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00766155
Information obtained from ClinicalTrials.gov on December 18, 2011

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