A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Cancer

Oral Topotecan As A Radiosensitizing Agent In Rectal Cancer


Lead sponsor: GlaxoSmithKline

Source GlaxoSmithKline
Brief Summary

Patients with rectal cancer who are candidates for pre-operative radiation therapy may be enrolled in the Phase I, single center study. Patients will have a full blood count, biochemistry, urinalysis, and ECG for safety evaluation. Sequential cohorts of three patients will be given increasing doses of oral topotecan and fixed doses of concurrent radiation (45 Gy) over five weeks. The starting dose of oral topotecan is 0.25 mg/m2 to be concomitantly administered with radiation (45 Gy) x 5 days every week unless the radiation is interrupted for Holidays/Weekends or toxicity requiring treatment delays occurs. A total of 25 doses are planned.

Overall Status Terminated
Start Date November 8, 2001
Completion Date August 11, 2006
Primary Completion Date August 11, 2006
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
To determine the MTD of oral topotecan in combination with pelvic radiation Up to 24 months
Secondary Outcome
Measure Time Frame
To evaluate the toxicity and potential efficacy of oral topotecan and concurrent pelvic radiation for the treatment of rectal cancer. To determine pathologic response to treatment and assessment of sphincter preservation. Up to 24 months
Enrollment 26

Intervention type: Drug

Intervention name: Topotecan

Description: Topotecan will be provided as capsules for oral administration and will be administered at least 3 hours before radiation therapy.

Arm group label: Subjects with rectal cancer

Other name: Hycamtin

Intervention type: Radiation

Intervention name: Radiation therapy

Description: For radiation therapy, subjects will receive 180 centigray (cGy) per fraction to a total dose of 4500 cGy to the pelvis using a 3 or 4 field technique and high energy photons (>=6 megavolt [mv]).

Arm group label: Subjects with rectal cancer



Inclusion Criteria:

- Patients with histologically confirmed rectal cancer.

- Candidates for preoperative radiotherapy.

- Primary tumor at least 3cm and clinical stage of T2, T3, or T4 and any N according to the Astler-Coller modification of the Dukes staging system.

- Eastern Cooperative Oncology Group (ECOG) performance status less than 2.

- Diagnosis of rectal cancer should be no more than 90 days from start of therapy.

- Evaluation at the H. Lee Moffitt Cancer Center.

- Recovery from prior surgery and life expectancy at least 3 months.

Exclusion Criteria:

- A primary tumor totally excised.

- Recurrent rectal cancer that failed initial treatment.

- Exposure to topotecan, infection, immunodeficiencies, conditions of the gastrointestinal (GI) tract which would affect absorption, medication that maintains motility/gastric emptying.

- Any concomitant malignancy within the last five years.

- Severe medical problems unrelated to the malignancy which would limit compliance with the study.

- Patients of child bearing potential.

- Not practicing adequate contraception.

- Patients who are pregnant or lactating.

- Use of an investigational drug within 30 days or 5 half-lives of the first dose.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
GSK Clinical Trials Study Director GlaxoSmithKline
facility GSK Investigational Site
Location Countries

United States

Verification Date

November 2017

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Arm group label: Subjects with rectal cancer

Arm group type: Experimental

Description: Subjects will be administered topotecan along with concomitant radiation for five days per week for five weeks. Topotecan doses will start at 0.25 milligrams per square meter (mg/m˄2) and will be escalated 0.15 mg/m˄2 for subsequent cohorts. To advance to the next dose level of topotecan, at least two subjects will have to complete therapy with oral topotecan without experiencing grade 3 or 4 toxicity for three weeks after the oral topotecan treatment.

Study Design Info

Allocation: Non-Randomized

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov