Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy Followed by Surgery in Treating Patients With Locally Advanced Cancer of the Rectum

National Cancer Institute (NCI)24 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically proven previously untreated adenocarcinoma of the rectum thatbegins within 12 cm of the anal verge by sigmoidoscopy and/or colonoscopy * 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 * No distant metastatic disease * Performance status - ECOG 0-2 * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * Bilirubin no greater than upper limit of normal (ULN) * SGOT/SGPT no greater than 2.5 times ULN * Creatinine no greater than 1.5 mg/dL * Creatinine clearance at least 60 mL/min * No active second malignancy except nonmelanomatous skin cancer or carcinoma in situ of the cervix * Patients are not considered to have an active second malignancy if they have completed therapy and are at less than 30% risk of relapse * No prior or concurrent evidence of neuropathy * No history of allergy to platinum compounds or antiemetics * Not pregnant or nursing * Fertile patients must use effective contraception * No prior fluorouracil or platinum-based therapy for any malignancy * No other concurrent chemotherapy * Hormonal therapy allowed only for non-disease related conditions (e.g., insulin for diabetes) OR intermittently as an antiemetic (e.g., dexamethasone) * No prior pelvic irradiation * No concurrent antiretroviral therapy (HAART) for HIV positive patients

Outcomes

Primary Outcomes

The maximum tolerated dose of oxaliplatin when delivered concurrently with 5-FU and external beam radiation in patients with locally advanced rectal adenocarcinomas

Time frame: 7 days

Progression-free survival

Will be estimated using the Kaplan-Meier method.

Time frame: From protocol entry until documented progression of disease or death from any cause, assessed up to 5 years

Pathological complete response rate

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.

Time frame: Up to 5 years

Latent toxicities graded using the Common Toxicity Criteria (CTC) version 2.0

Time frame: Up to 5 years

Oxaliplatin, Fluorouracil, and External-Beam Radiation Therapy Followed by Surgery in Treating Patients With Locally Advanced Cancer of the Rectum

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes