Phase I Study of Preoperative Intensity Modulated Radiation Therapy (IMRT) With Incorporated Boost and Oral Capecitabine in Locally Advanced Rectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
Phase I Study of Preoperative Intensity Modulated Radiation Therapy (IMRT) With Incorporated Boost and Oral Capecitabine in Locally Advanced Rectal Cancer
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of neoadjuvant boost intensity-modulated
radiotherapy when combined with capecitabine before surgery in patients with locally
advanced rectal cancer.
Secondary
- Determine the pathologic tumor response in patients treated with this regimen.
- Determine the quality of life of patients treated with this regimen.
OUTLINE: This is a dose-escalation study of boost intensity-modulated radiotherapy (IMRT).
Patients undergo neoadjuvant IMRT with incorporated boost once daily 5 days a week for 5
weeks. Beginning on the first day of radiotherapy, patients receive oral capecitabine twice
daily 7 days a week for 5 weeks. Patients undergo surgical resection 4-8 weeks after
completion of chemoradiotherapy.
Cohorts of 3-6 patients undergo escalating doses of boost IMRT until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 3
of 6 patients experience dose-limiting toxicity.
Quality of life is assessed at baseline, at week 5 of chemoradiotherapy, before surgery, and
then at 1, 3, and 12 months after surgery.
Patients are followed at 1, 3, and 12 months after surgery.
PROJECTED ACCRUAL: Approximately 3-15 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed primary adenocarcinoma of the rectum
- Distal border of the tumor within 12 cm of the anal verge by proctoscopic exam
- Clinical stage T3-4, N1-2 (stage II or III) disease by 2 of the following tests:
- Physical exam
- Transrectal ultrasound
- Pelvic CT scan
- Pelvic MRI
- No clinical evidence of metastatic disease
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- No known, uncontrolled coagulopathy
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGOT and SGPT ≤ 1.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
Renal
- Creatinine ≤ 1.5 times normal
- Creatinine clearance > 50 mL/min
Cardiovascular
- No clinically significant cardiac disease
- No congestive heart failure
- No symptomatic coronary artery disease
- No poorly controlled cardiac arrhythmias
- No myocardial infarction within the past year
Gastrointestinal
- No active inflammatory bowel disease
- No lack of physical integrity of the upper gastrointestinal tract
- No malabsorption syndrome
Other
- No other prior or concurrent malignancy except inactive, non-invasive carcinoma of
the cervix or non-melanoma skin cancer
- No concurrent serious, uncontrolled infection(s)
- No prior unanticipated severe reaction to fluoropyrimidine therapy
- No known sensitivity to fluorouracil
- No prior uncontrolled seizures
- No CNS disorders that would preclude study participation
- No other medical or psychiatric condition that would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 3 months after study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No prior immunotherapy for rectal cancer
Chemotherapy
- No prior chemotherapy for rectal cancer
Endocrine therapy
- Not specified
Radiotherapy
- No prior radiotherapy for rectal cancer
- No prior pelvic radiotherapy
Surgery
- More than 4 weeks since prior major surgery and recovered
- No prior surgery for rectal cancer
Other
- More than 4 weeks since prior participation in another investigational drug study
- No concurrent celecoxib
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Acute toxicity by CTCAE at 6 weeks following study completion
Safety Issue:
Yes
Principal Investigator
Gary Freedman, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fox Chase Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000365462
NCT ID:
NCT00084591
Start Date:
December 2003
Completion Date:
February 2007
Related Keywords:
- Colorectal Cancer
- stage II rectal cancer
- stage III rectal cancer
- adenocarcinoma of the rectum
- Rectal Neoplasms
- Colorectal Neoplasms
Name | Location |
|---|---|
| Fox Chase Cancer Center | Philadelphia, Pennsylvania 19111 |
