Oral Topotecan As A Radiosensitizing Agent In Rectal Cancer

GlaxoSmithKline (GSK)

Status and phase: Terminated; Phase 1

Conditions: Carcinoma, Renal Cell

Treatments: Radiation: Radiation therapy; Drug: Topotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00158886

104864/517

Details and patient eligibility

About

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.

Enrollment: 26 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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26 participants in 1 patient group

Subjects with rectal cancer

Experimental group

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.

Treatment:

Drug: Topotecan

Radiation: Radiation therapy