Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-Surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).
18 Years
80 Years
Both
Colorectal Cancer
Trial Information
Phase II Multicenter Study of the Impact of the Therapeutic Sequence of Radiochemotherapy (50 Gy + Capecitabine + Oxaliplatin + Cetuximab) Followed by Total Mesorectal Excision Surgery Then Post-Surgery Chemotherapy (FOLFOX 4 + Cetuximab) in Synchronous Locally Advanced or Metastatic Cancers of the Rectum With Metastases Resectable From the Start (T3-4 Nx or T2 N+ M1).
OBJECTIVES:
Primary
- Determine the complete remission rate at 6 months after neoadjuvant radiotherapy,
capecitabine, and oxaliplatin (XELOX), and cetuximab followed by surgery, adjuvant
FOLFOX 4, and cetuximab in patients with synchronous locally advanced or metastatic
cancer of the rectum with resectable metastases (T3-4 Nx or T2 N+ M1).
Secondary
- Determine progression-free survival.
- Determine overall survival.
- Assess toxicities.
- Evaluate objective response in patients with measurable metastases.
- Determine the rate of local recurrence.
- Evaluate the downstaging and downsizing of patients with operable disease.
- Evaluate surgical complications in patients with operable disease.
- Evaluate biological markers predictive of response to cetuximab.
OUTLINE: This is a multicenter study.
- Neoadjuvant therapy: Patients undergo radiotherapy for 5 weeks and receive concurrent
oral capecitabine twice daily on days 1-5 of each week and oxaliplatin IV over 2 hours
on day 1 of each week (XELOX). Patients also receive cetuximab IV on day 1 of the first
week and on days 1-7 of weeks 2-5.
- Surgery: At 6 weeks after completing chemoradiotherapy, patients with resectable
disease undergo surgery comprising total mesorectal excision. Patients with progressive
disease, nonresectable tumor, or who require R2 surgery are removed from the study.
- Adjuvant therapy: Patients who undergo surgery, with or without removal of metastases,
receive FOLFOX 4, comprising oxaliplatin IV over 2 hours, fluorouracil IV over 46
hours, and leucovorin calcium IV on day 1, and cetuximab IV. Treatment repeats every 2
weeks for up to 6 courses (approximately 3 months). Patients who have not undergone
prior surgical resection of metastases may have surgery to remove metastases after
completing this second regimen of chemotherapy.
After completion of study therapy, patients are followed periodically for up to 5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the rectum
- Locally advanced (T3-4 Nx) or metastatic (T2 N+ M1) synchronous disease
- Metastases must be resectable
- Primary tumor examined by endorectal echography and MRI
- Measurable disease by thoraco-abdomino-pelvic scanner
- Disease considered susceptible to treatment with radiotherapy and chemotherapy
- No diffuse metastases considered nonresectable
- No acute occlusion not caused by colostomy
PATIENT CHARACTERISTICS:
Inclusion criteria:
- ECOG performance status 0-2
- WBC ≥ 4,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
- Creatinine ≤ 130 µmol/L
- Transaminases ≤ 5 times upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients of must use effective contraception
Exclusion criteria:
- Contraindication to therapy with capecitabine, oxaliplatin, cetuximab, and/or
radiotherapy
- Impossible to perform translational analyses
- Uncontrolled severe illness
- Severe renal or hepatic insufficiency
- Cardiac insufficiency or symptomatic coronary disease
- Sensitive peripheral neuropathy
- Uncontrolled diabetes
- Other malignancy within the past 10 years except previously treated basal cell skin
cancer or carcinoma in situ of the cervix
- Impossible to participate in study due to geographic, social, or psychiatric reasons
- Patients who are under supervision or incarcerated
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior anticancer chemotherapy or radiotherapy for this cancer
- No therapy with coumarin anticoagulants, phenytoin, sorivudine, brivudine, antacids,
or allopurinol
- No concurrent participation in another therapeutic study or receiving another
experimental drug
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Primary Purpose: Treatment
Outcome Measure:
Complete remission at ≥ 6 months by abdomino-pelvic-thoracic scan and a pelvic MRI
Safety Issue:
No
Principal Investigator
David Azria, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Centre Val d'Aurelle - Paul Lamarque
Authority:
Unspecified
Study ID:
CDR0000565937
NCT ID:
NCT00541112
Start Date:
July 2007
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage III rectal cancer
- stage IV rectal cancer
- adenocarcinoma of the rectum
- Rectal Neoplasms
- Colorectal Neoplasms
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