A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma
This is an open-label, single center, phase I study designed to determine the MTD or oral
topotecan as a radiosensitizing agent in the treatment of rectal cancer patients.
Sequential cohorts of three patients will be given increasing doses of oral topotecan and
fixed doses of concurrent radiation (45GY) over five weeks. The starting dose of oral
topotecan is 0.25mg/m2 to be concomitantly administered with radiation (45Gy) x 5 days every
week unless the radiation is interrupted for Holidays/Weekends or toxicity requiring
treatment delays occurs.
A total of 25 doses is planned. Doses will be escalated in 0.15 mg/m2 increments thereafter
in subsequent cohorts. Topotecan will be administered immediately before daily radiation.
All patients will undergo a rectal biopsy before treatment begins and during treatment.
Tissue will be submitted to H. Lee Moffitt Cancer Center for tumor marker assays. Tissue
from the excised tumor at the time of surgery will also be sent for the same studies.
Between day 10 and 14 of treatment, colonoscopy/sigmoidoscopy is mandatory to ensure having
a quantitative estimate of the tumor shrinkage and to obtain a repeat rectal biopsy. All
patients will undergo radiation therapy concurrently with oral topotecan. Patients will
receive 180 cGY per fraction to a total dose of 4500cGy(conventional fractionation) to the
pelvis using a 3 or 4 filed technique and high energy photons. Standardized fields for
rectal cancer will be used to include the true pelvis (mid sacrum to at least 2-3
centimeters below the inferior aspect of the tumor volume).
Patients will undergo surgery-either a low anterior resection, abdominoperineal resection or
local excision. All patients will be offered postoperative adjuvant chemotherapy consisting
of 5-Fluorouracil (F-FU) 350 mg/m2/day i.v. for 5 days administered every 28 days times four
cycles. Immediately prior to the administration of 5-FU, leucovorin will be administered at
a dose of 20 mg/m2/day i.v. push daily for 5 days every 28 days times four cycles.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum Tolerated Dose of topotecan
William Dinwoodie, MD
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center & Research Institute||Tampa, Florida 33612|