A Multicentre Randomised Phase II Clinical Trial Comparing Oxaliplatin (Eloxatin), Capecitabine (Xeloda) and Pre-Operative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision for the Treatment of Patients With Magnetic Resonance Imaging (MRI) Defined High Risk Rectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A Multicentre Randomised Phase II Clinical Trial Comparing Oxaliplatin (Eloxatin), Capecitabine (Xeloda) and Pre-Operative Radiotherapy With or Without Cetuximab Followed by Total Mesorectal Excision for the Treatment of Patients With Magnetic Resonance Imaging (MRI) Defined High Risk Rectal Cancer
OBJECTIVES:
- Compare the pathological complete response rate at total mesorectal excision in
patients with high-risk rectal cancer treated with neoadjuvant therapy comprising
oxaliplatin, capecitabine, and radiotherapy with or without cetuximab.
OUTLINE: This is a multicenter, open-label, randomized, controlled study. Patients are
stratified according to participating center and presence of T4 disease (yes vs no).
Patients are randomized to 1 of 2 treatment arms.
- Arm I:
- Neoadjuvant chemotherapy: Patients receive oxaliplatin IV over 2 hours on days 1,
22, 43, and 64 and oral capecitabine twice daily on days 1-14, 22-35, 43-56, and
64-77.
- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy once daily on days
85-89, 92-96, 99-103, 106-110, 113-117, and 120-124 and receive oral capecitabine
twice daily on days 85-126.
- Surgery: Four to six weeks after completion of chemoradiotherapy, patients undergo
total mesorectal excision (TME).
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin
IV over 2 hours on days 1, 22, 43, and 64 and oral capecitabine twice daily on
days 1-14, 22-35, 43-56, and 64-77.
- Arm II:
- Neoadjuvant therapy: Patients receive oxaliplatin and capecitabine as in arm I
neoadjuvant chemotherapy and cetuximab IV over 1-2 hours on days 1, 8, 15, 22, 29,
36, 43, 50, 57, 64, 71, and 78.
- Neoadjuvant chemoradiotherapy: Patients undergo radiotherapy and receive
capecitabine as in arm I neoadjuvant chemoradiotherapy and cetuximab IV over 1
hour on days 85, 92, 99, 106, 113, and 120.
- Surgery: Four to six weeks after completion of chemoradiotherapy patients undergo
TME as in arm I.
- Adjuvant therapy: Beginning 6-8 weeks after surgery, patients receive oxaliplatin
and capecitabine as in arm I adjuvant chemotherapy and cetuximab IV over 1 hour on
days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78.
In both arms, treatment continues in the absence of disease progression or unacceptable
toxicity.
Quality of life is assessed periodically.
After completion of study treatment, patients are followed every 3 months for 1 year, every
6 months for 2 years, and then annually for 2 years.
PROJECTED ACCRUAL: A total of 164 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma or undifferentiated non-small cell carcinoma
of the rectum
- MRI-defined high-risk, operable disease, defined by ≥ 1 of the following:
- Tumors within 1 mm of mesorectal fascia (i.e., circumferential resection margin
threatened or involved)
- T3 tumors at or below levators
- Tumors extending ≥ 5 mm into perirectal fat
- T4 tumors
- Presence of extramural venous invasion (primary tumor is therefore at least T3)
- No evidence of metastatic disease by CT scan of the chest and abdomen or, if
required, by positron emission tomography scan or biopsy
- No rectal cancer that is unlikely to be operable even after neoadjuvant treatment
(i.e., tumor involving the internal iliac vessels)
- No T1-2 rectal cancer, in the absence of other high-risk factors
- T2 tumors within 1 mm of mesorectal fascia allowed
- No recurrent disease
PATIENT CHARACTERISTICS:
- WHO performance status 0-2
- Life expectancy > 3 months
- WBC > 3,000/mm³
- Absolute neutrophil count > 1,500/mm³
- Platelet count > 100,000/mm³
- Bilirubin < 1.5 times upper limit of normal (ULN)
- Transaminases < 2.5 times ULN
- Creatinine normal OR creatinine clearance > 50 mL/min
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No concurrent uncontrolled medical condition
- No other active malignant disease within the past 10 years except nonmelanoma skin
cancer or carcinoma in situ of the cervix
- No contraindications to MRI (e.g., pacemaker)
- No medical or psychiatric conditions that would preclude informed consent
- No known malabsorption syndrome or lack of physical integrity of the upper
gastrointestinal tract
- No clinically significant (i.e., active) cardiac disease, including any of the
following:
- Congestive heart failure
- Symptomatic coronary artery disease
- Cardiac dysrhythmia (e.g., atrial fibrillation, even if controlled with
medication)
- Myocardial infarction within the past 12 months
- No symptoms or history of peripheral neuropathy
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy, radiotherapy, or investigational treatment for rectal cancer
- No other concurrent cytotoxic agents or investigational drugs
- No concurrent sorivudine or sorivudine analogues (e.g., brivudine)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Pathological complete response rate at time of total mesorectal excision (TME)
Safety Issue:
No
Principal Investigator
David Cunningham, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Royal Marsden NHS Foundation Trust
Authority:
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Study ID:
CDR0000503948
NCT ID:
NCT00383695
Start Date:
September 2005
Completion Date:
Related Keywords:
- Colorectal Cancer
- adenocarcinoma of the rectum
- stage I rectal cancer
- stage II rectal cancer
- stage III rectal cancer
- Rectal Neoplasms
- Colorectal Neoplasms
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