Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy Followed by Surgery in Treating Patients With Locally Advanced Cancer of the Rectum
- Conditions
- Adenocarcinoma of the RectumStage II Rectal CancerStage III Rectal Cancer
- Interventions
- Registration Number
- NCT00006094
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy, radiation therapy, and surgery may be a more effective treatment for cancer of the rectum. Phase II trial to study the effectiveness of combining oxaliplatin, fluorouracil, and external-beam radiation therapy followed by surgery in treating patients who have locally advanced cancer of the rectum
- Detailed Description
PRIMARY OBJECTIVES:
I. Determine the maximum tolerated dose of oxaliplatin when combined with fluorouracil and external beam radiotherapy in patients with locally advanced adenocarcinoma of the rectum.
(Phase I closed to accrual effective 03/27/2003). II. Determine the pathological response rate in patients treated with this preoperative regimen and surgical resection.
III.Determine the late toxicity of this preoperative regimen in these patients. IV. Determine, in a preliminary manner, the progression-free survival, local control, and overall survival in patients treated with this regimen.
OUTLINE: This is a dose-escalation, multicenter study of oxaliplatin.
Patients receive oxaliplatin IV over 1 hour on day 1, fluorouracil IV continuously on days 1-7, and radiotherapy on days 1-5. Treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of oxaliplatin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are treated at that dose level in the phase II portion of the study. (Phase I closed to accrual effective 03/27/2003). Patients may undergo radical resection of rectal tumor within 4-6 weeks after completion of chemoradiotherapy.
Patients are followed every 3 months for 2 years and then every 6 months for 3 years.
PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for phase I of the study (phase I closed to accrual effective 03/27/2003) and a total of 19 patients will be accrued for phase II of the study within 12-18 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
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Histologically proven previously untreated adenocarcinoma of the rectum thatbegins within 12 cm of the anal verge by sigmoidoscopy and/or colonoscopy
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Locally advanced disease defined as any of the following:
- Fixed or immovable tumor on physical exam
- T4 disease with invasion of adjacent structures (e.g., pelvic sidewall, sacral pelvis, bladder, or prostate) by CT scan, rectal ultrasound, or MRI
- T3 disease with invasion through the wall of the muscularis propria by transrectal ultrasound, CT scan, or MRI
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No distant metastatic disease
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Performance status - ECOG 0-2
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Granulocyte count at least 1,500/mm^3
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Platelet count at least 100,000/mm^3
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Bilirubin no greater than upper limit of normal (ULN)
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SGOT/SGPT no greater than 2.5 times ULN
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Creatinine no greater than 1.5 mg/dL
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Creatinine clearance at least 60 mL/min
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No active second malignancy except nonmelanomatous skin cancer or carcinoma in situ of the cervix
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Patients are not considered to have an active second malignancy if they have completed therapy and are at less than 30% risk of relapse
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No prior or concurrent evidence of neuropathy
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No history of allergy to platinum compounds or antiemetics
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Not pregnant or nursing
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Fertile patients must use effective contraception
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No prior fluorouracil or platinum-based therapy for any malignancy
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No other concurrent chemotherapy
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Hormonal therapy allowed only for non-disease related conditions (e.g., insulin for diabetes) OR intermittently as an antiemetic (e.g., dexamethasone)
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No prior pelvic irradiation
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No concurrent antiretroviral therapy (HAART) for HIV positive patients
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (oxaliplatin, fluorouracil, EBRT) oxaliplatin Patients receive oxaliplatin IV over 1 hour on day 1, fluorouracil IV continuously on days 1-7, and radiotherapy on days 1-5. Treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Treatment (oxaliplatin, fluorouracil, EBRT) external beam radiation therapy Patients receive oxaliplatin IV over 1 hour on day 1, fluorouracil IV continuously on days 1-7, and radiotherapy on days 1-5. Treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Treatment (oxaliplatin, fluorouracil, EBRT) fluorouracil Patients receive oxaliplatin IV over 1 hour on day 1, fluorouracil IV continuously on days 1-7, and radiotherapy on days 1-5. Treatment repeats weekly for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.
- Primary Outcome Measures
Name Time Method Progression-free survival From protocol entry until documented progression of disease or death from any cause, assessed up to 5 years Will be estimated using the Kaplan-Meier method.
The maximum tolerated dose of oxaliplatin when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinomas 7 days Pathological complete response rate Up to 5 years The new regimen will be considered worthy of further investigation if 5 or greater CR's are observed among the 25 patients treated at the MTD. Assuming the new regimen will result in a 30% CR rate, the probability of observing 5 or greater CR's in 25 patients studied is 0.91. For an underlying CR rate of 0.25 this probability is 0.79. The probability of observing 5 or greater CR's if the underlying CR rate is 0.10 is 0.10.
Latent toxicities graded using the Common Toxicity Criteria (CTC) version 2.0 Up to 5 years
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Cancer and Leukemia Group B
🇺🇸Chicago, Illinois, United States