Preoperative Chemoradiotherapy and Postoperative Chemotherapy With Capecitabine and Oxaplatin vs.Capecitabine Alone in Locally Advanced Rectal Cancer (PETACC-6)
18 Years
N/A
Both
Colorectal Cancer
Trial Information
Preoperative Chemoradiotherapy and Postoperative Chemotherapy With Capecitabine and Oxaplatin vs.Capecitabine Alone in Locally Advanced Rectal Cancer (PETACC-6)
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Disease-free survival
Safety Issue:
No
Principal Investigator
Hans-Joachim Schmoll, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Martin-Luther-Universität Halle-Wittenberg
Authority:
United States: Federal Government
Study ID:
CDR0000614916
NCT ID:
NCT00766155
Start Date:
August 2008
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage II rectal cancer
- stage III rectal cancer
- adenocarcinoma of the rectum
- Rectal Neoplasms
- Colorectal Neoplasms
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