A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients With Clinical T4 Rectal Cancer
18 Years
N/A
Both
Colorectal Cancer
Trial Information
A Phase II Feasibility Translational Research Trial of Induction Chemotherapy Followed by Concomitant Chemoradiation in Patients With Clinical T4 Rectal Cancer
OBJECTIVES:
- Determine the feasibility of obtaining a pre-treatment determination of intratumoral
molecular markers (TS, DPD, and ERCC-1) for use in selection of the appropriate regimen
for induction cytotoxic combination chemotherapy in patients with cT3-4 rectal
adenocarcinoma.
- Determine the response probability (unconfirmed, complete and partial) in patients
treated with targeted induction cytotoxic chemotherapy.
- Determine the toxicity of targeted induction cytotoxic chemotherapy and
chemoradiotherapy in these patients.
- Determine the response probability in these patients treated with chemoradiotherapy.
OUTLINE: This is a multicenter study.
- Induction chemotherapy: Patients are assigned to 1 of 3 treatment groups based on
molecular analysis of the pretreatment tumor specimen.
- Group I (lower likelihood of resistance to a fluorouracil-based regimen): Patients
receive irinotecan IV over 90 minutes and leucovorin calcium IV over 2 hours on
day 1 and fluorouracil IV over 46 hours beginning on day 1.
- Group II (higher likelihood of resistance to a fluorouracil-based regimen):
Patients receive oxaliplatin IV over 2 hours and irinotecan IV over 90 minutes on
day 1.
- Group III (high likelihood of sensitivity to oxaliplatin and fluorouracil
therapy): Patients receive oxaliplatin IV over 90 minutes and leucovorin calcium
IV over 2 hours on day 1 and fluorouracil IV over 46 hours beginning on day 1.
Treatment in all groups repeats every 2 weeks for 4 courses in the absence of disease
progression or unacceptable toxicity.
Patients are evaluated for response approximately 2 weeks after the completion of induction
chemotherapy. Patients with stable disease or better receive chemoradiotherapy.
- Chemoradiotherapy: Beginning approximately 3 weeks after the completion of induction
chemotherapy, patients receive oral capecitabine twice daily continuously for 5 weeks
and concurrent radiotherapy once daily 5 days a week for 5 weeks.
After chemoradiotherapy, patients may undergo attempted surgical resection at the discretion
of the treating physician.
Patients are followed every 3 months for 1 year and then every 6 months for 2 years.
PROJECTED ACCRUAL: A total of 10-65 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed primary adenocarcinoma of the rectum
- Locally advanced disease (clinical T3-4, N0-2, M0) based on at least 1 of the
following criteria:
- Clinically fixed tumors on rectal examination with tumor adherent to the pelvic
sidewall and/or sacrum
- Sciatica attributed to sacral root invasion with CT scan/MRI evidence of the
lack of clear tissue plane is considered evidence of fixation
- Hydronephrosis on CT scan or intravenous pyelogram of ureteric or bladder
invasion by cystoscopy and cytology or biopsy
- Invasion into the prostate, vagina, or uterus
- Transmural penetration of tumor through the muscularis propria as evidenced by CT
scan or MRI and endorectal ultrasound
- Distal border of the tumor must be at or below the peritoneal reflection (within 12
cm of the anal verge) by proctoscopic examination
- Measurable disease by x-ray, scans, or physical examination
- Available tumor tissue to determine molecular profile of the tumor before study
treatment
- No clinical evidence of high-grade (lumen diameter < 1 cm) large bowel obstruction
unless a diverting colostomy has been performed
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Zubrod 0-2
Life expectancy
- Not specified
Hematopoietic
- WBC ≥ 3,500/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥100,000/mm^3
Hepatic
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGOT or SGPT ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2.5 times ULN
Renal
- See Disease Characteristics
- Creatinine ≤ 1.5 times ULN OR
- Estimated creatinine clearance > 50 mL/min
Cardiovascular
- No significant cardiac disease
- No recent myocardial infarction
Gastrointestinal
- See Disease Characteristics
- Able to swallow oral medication
- No active inflammatory bowel disease
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No prior unanticipated severe reaction to study drugs
- No known dihydropyrimidine dehydrogenase deficiency
- No serious uncontrolled infection
- No other serious medical illness that would preclude study treatment
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- No prior chemotherapy for colon or rectal cancer
Endocrine therapy
- Not specified
Radiotherapy
- No prior pelvic radiotherapy
- No prior intra-operative radiotherapy or brachytherapy
- No concurrent intra-operative radiotherapy or brachytherapy
- No concurrent intensity-modulated radiotherapy
Surgery
- See Disease Characteristics
- See Radiotherapy
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Response (confirmed and unconfirmed response, complete response, partial response)
Safety Issue:
No
Principal Investigator
Charles R. Thomas, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Texas Health Science Center at San Antonio
Authority:
United States: Federal Government
Study ID:
CDR0000334469
NCT ID:
NCT00070434
Start Date:
August 2004
Completion Date:
Related Keywords:
- Colorectal Cancer
- stage II rectal cancer
- stage III rectal cancer
- adenocarcinoma of the rectum
- Adenocarcinoma
- Rectal Neoplasms
- Colorectal Neoplasms
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