Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
Randomized Phase II Trial Of Neoadjuvant Combined Modality Therapy For Locally Advanced Rectal Cancer
OBJECTIVES:
- Compare the pathologic complete response rate in patients with locally advanced rectal
cancer undergoing surgical resection treated with 2 different regimens of neoadjuvant
chemoradiotherapy and adjuvant chemotherapy.
- Compare the time to treatment failure and patterns of failure in patients treated with
these regimens.
- Compare the incidence of hematologic and non-hematologic grade 3-4 toxicity
(preoperatively, postoperatively, and overall) in patients treated with these regimens.
- Compare the quality of life of patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
clinical stage of tumor (T3 vs T4). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive neoadjuvant therapy comprising radiotherapy once daily, 5 days
a week, for 6 weeks and concurrent oral capecitabine twice daily (5 days a week) for 6
weeks and irinotecan IV over 1 hour on days 1, 8, 22, and 29.
Patients undergo surgical resection 4-8 weeks after completing radiotherapy.
Beginning 4-6 weeks after surgery, patients receive adjuvant chemotherapy comprising
oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil
IV continuously over 46 hours beginning on day 1. Treatment repeats every 14 days for a
total of 9 courses.
- Arm II: Patients receive neoadjuvant therapy comprising radiotherapy and capecitabine
as in arm I and oxaliplatin IV over 2 hours on days 1, 8, 15, 22, and 29.
Patients undergo surgical resection 4-8 weeks after completing radiotherapy.
Beginning 4-6 weeks after surgery, patients receive adjuvant chemotherapy comprising
oxaliplatin, leucovorin calcium, and fluorouracil as in arm I adjuvant chemotherapy.
Treatment repeats every 14 days for a total of 9 courses.
Quality of life is assessed at baseline, within 1 week after completion of radiotherapy,
within 1 week after completion of adjuvant chemotherapy (12 months), and then at 24 months.
Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then
annually thereafter.
PROJECTED ACCRUAL: A total of 141 patients (approximately 70 per treatment arm) will be
accrued for this study within 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of adenocarcinoma of the rectum
- Clinical stage T3 or T4 disease by endorectal ultrasound or physical examination
(for T4 lesions only)
- Tumor originating at or below 12 cm from the anal verge
- No extension of disease into the anal canal
- No evidence of distant metastases
- No synchronous primary colon carcinomas except T1 lesions
- Potentially resectable en bloc disease
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Zubrod 0-2
Life expectancy
- Not specified
Hematopoietic
- Absolute neutrophil count > 1,500/mm^3
- Platelet count > 100,000/mm^3
Hepatic
- AST < 2.5 times upper limit of normal (ULN)
- Alkaline phosphatase < 2.5 times ULN
- Bilirubin ≤ 1.5 times ULN
- No known uncontrolled coagulopathy
Renal
- Creatinine clearance > 50 mL/min
Cardiovascular
- No congestive heart failure
- No symptomatic coronary artery disease
- No uncontrolled cardiac arrhythmias
- No myocardial infarction within the past year
- No other clinically significant cardiac disease
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 30 days after
completion of study treatment
- No concurrent serious uncontrolled infection
- No malabsorption syndrome
- No lack of physical integrity of the upper gastrointestinal tract
- No evidence of uncontrolled seizures, CNS disorders, or psychiatric disability that,
judged by the investigator, is clinically significant, precludes giving informed
consent, or interferes with compliance of oral drug intake
- No other malignancy within the past 5 years except nonmelanoma skin cancer, carcinoma
in situ of the cervix, or ductal carcinoma in situ of the breast
- No other serious uncontrolled medical condition that would preclude study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent routine prophylactic filgrastim (G-CSF)
Chemotherapy
- No prior anticancer chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy to the pelvis
- No concurrent intensity-modulated radiotherapy
Surgery
- More than 4 weeks since prior major surgery
Other
- More than 4 weeks since prior participation in another clinical trial
- No concurrent cimetidine
- No concurrent sorivudine or brivudine
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Pathologic complete response rate
Safety Issue:
No
Principal Investigator
Neal J. Meropol, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fox Chase Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000350136
NCT ID:
NCT00081289
Start Date:
March 2004
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage III rectal cancer
- adenocarcinoma of the rectum
- stage II rectal cancer
- Rectal Neoplasms
- Colorectal Neoplasms
Name | Location |
|---|---|
| University of California Davis Cancer Center | Sacramento, California 95817 |
| Baptist-South Miami Regional Cancer Program | Miami, Florida 33176 |
| Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton | Marlton, New Jersey 08053 |
| Ingalls Cancer Care Center at Ingalls Memorial Hospital | Harvey, Illinois 60426 |
| Northeast Radiation Oncology Center | Dunmore, Pennsylvania 18512 |
