A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer
18 Years
75 Years
Both
Colorectal Cancer
Trial Information
A Phase I/II Study of Weekly Intravenous Oxaliplatin in Combination With Oral Daily Capecitabine and Radiation Therapy in the Neoadjuvant Treatment of Rectal Cancer
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of neoadjuvant oxaliplatin and capecitabine when
combined with radiotherapy in patients with locally advanced adenocarcinoma of the
rectum. (Phase I closed to accrual as of 06/2005.)
- Determine the rate of complete pathological response in patients treated with this
regimen.
Secondary
- Determine the overall survival of patients treated with this regimen.
- Determine the rate of local and overall failure in patients treated with this regimen.
- Determine the utility of TS, TP, DPD, ERCC-1, and apoptosis to predict response in
patients treated with this regimen.
- Determine the rate of pathologic down-staging in patients treated with this regimen.
- Determine the safety and toxicity of this regimen in these patients.
- Determine the rate of sphincter-saving rectal surgery in patients treated with this
regimen who had been deemed candidates for abdominoperineal resection at diagnosis.
OUTLINE: This is a multicenter, phase I (phase I closed to accrual as of 06/2005),
dose-escalation study of oxaliplatin and capecitabine followed by a phase II study.
- Phase I (closed to accrual as of 06/2005): Patients undergo radiotherapy once daily 5
days a week for 5.5 weeks and receive oral capecitabine twice daily on days
radiotherapy is administered. Beginning on day 1 of radiotherapy, patients also receive
oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin and capecitabine until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
- Phase II: Patients undergo radiotherapy and receive capecitabine and oxaliplatin as in
phase I at the MTD.
All patients undergo curative-intent surgery 6-8 weeks after the completion of
chemoradiotherapy.
Patients are followed every 3 months for 3 years and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 31-40 patients (6-15 for phase I [phase I closed to accrual as
of 06/2005] and 25 for phase II) will be accrued for this study within 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adenocarcinoma of the rectum
- Tumor involving the distal 12 cm of the rectum (above the anal verge)
- Clinically staged by endoscopic ultrasound with one of the following criteria:
- T3-T4 disease
- Evidence of lymph node involvement, defined by the presence of ≥ 1 enlarged
peri-rectal lymph node (≥ 1 cm in size)
- No known distant metastases
PATIENT CHARACTERISTICS:
Age
- 18 to 75
Performance status
- ECOG 0-1 OR
- Karnofsky 70-100%
Life expectancy
- More than 1 year
Hematopoietic
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Bilirubin normal
- AST and ALT ≤ 2.5 times upper limit of normal
Renal
- Creatinine normal OR
- Creatinine clearance ≥ 60 mL/min
Cardiovascular
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
Other
- Able to receive oral medication
- No other malignancy within the past 5 years except nonmelanoma skin cancer
- No prior or concurrent significant neuropathy
- No prior allergic reaction attributed to compounds of similar chemical or biological
composition to study drugs
- No ongoing or active infection
- No other concurrent uncontrolled illness
- No psychiatric illness or social situation that would preclude study compliance
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective double-method contraception during and for 3
months after study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent granulocyte-stimulating factors
Chemotherapy
- No prior chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior pelvic radiotherapy
Surgery
- Not specified
Other
- No other concurrent investigational agents
- No other concurrent anticancer agents or therapies
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete pathological response rate at time of surgery
Outcome Time Frame:
Time of surgery
Safety Issue:
No
Principal Investigator
Marwan Fakih, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
I 10803
NCT ID:
NCT00086931
Start Date:
September 2003
Completion Date:
May 2010
Related Keywords:
- Colorectal Cancer
- adenocarcinoma of the rectum
- stage III rectal cancer
- stage II rectal cancer
- Rectal Neoplasms
- Colorectal Neoplasms
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
