Phase I Study of Preoperative Radiation Therapy With Concurrent Protracted Continuous Infusion 5-FU and Dose Escalating Oxaliplatin Followed by Surgery, 5-FU, and Leucovorin for Locally Advanced (T3 and T4) Rectal Adenocarcinoma
I. To identify maximally tolerated dose (MTD) and dose limiting toxicity (DLT) of
oxaliplatin when combined preoperatively with concurrent radiation therapy (XRT) and
fluorouracil (5-FU) by PVI.
II. To evaluate the resection rate for T4 rectal cancers, the pathologic CR rate for T3 and
T4 rectal cancers, and the expected versus actual type of resection (APR vs. LAR vs.
III. To make preliminary observations of patient survival and patterns of recurrence for
this treatment combination.
IV. To evaluate anastomotic and sphincter function following pre-op combined modality
OUTLINE: This is a dose-escalation study of preoperative oxaliplatin.
Patients receive fluorouracil IV continuously with concurrent radiotherapy for 5.5 weeks.
Patients also receive oxaliplatin IV over 2 hours on day 1 of weeks 1, 3, and 5.
Cohorts of 5 patients each receive escalating doses of oxaliplatin until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which
at least 2 of 5 patients experience dose-limiting toxicity. Additional patients are treated
at the MTD.
Patients undergo surgery 6-8 weeks after completing preoperative chemotherapy and
radiotherapy. The surgical procedure is determined by the extent of the tumor before
preoperative therapy. The type of operative procedure may be abdominoperineal resection, low
anterior resection (LAR), or LAR/coloanal anastomosis.
Postoperative chemotherapy begins within 6 weeks after surgery, comprising leucovorin
calcium and fluorouracil IV on days 1-5. Treatment repeats every 21 days for 4 courses.
Patients are followed every 3 months for 2.5 years, every 6 months for 3 years, then
annually for 5 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of oxaliplatin when combined with radiation therapy and fluorouracil based on the incidence of DLT as assessed by CTC version 2.0
Eastern Cooperative Oncology Group
United States: Food and Drug Administration
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