A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma|
- Maximum Tolerated Dose (MTD) of Topotecan [ Time Frame: up to 5 weeks ] [ Designated as safety issue: Yes ]Dose escalation to determine MTD that can be given with radiation.
- Side Effect Profile of Topotecan [ Time Frame: Up to 5 weeks ] [ Designated as safety issue: Yes ]Review of adverse events
- Response Rate [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]To determine pathologic response to treatment and assessment of sphincter preservation.
|Study Start Date:||November 2001|
|Study Completion Date:||January 2008|
|Primary Completion Date:||January 2008 (Final data collection date for primary outcome measure)|
Experimental: Dose Escalation and Radiation, Followed by Surgery
Preoperative treatment with radiation and oral topotecan for up to 5 weeks, followed by surgery.
Preoperative treatment: oral topotecan 5 days per week for up to 5 weeksProcedure: radiation
Preoperative radiationProcedure: surgery
surgery to remove tumor 4 to 8 weeks following completion of preoperative treatment
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00215956
|United States, Florida|
|H. Lee Moffitt Cancer Center & Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||William Dinwoodie, MD||H. Lee Moffitt Cancer Center and Research Institute|