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

NCT00215956 | Completed Phase 1

• 2 other identifiers: MCC-12349USFIRB#5881
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Rectal Neoplasms

Keywords

Topotecan; Rectal Neoplasms; Radiosensitizing

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (MTD) of Topotecan

  Dose escalation to determine MTD that can be given with radiation.

  up to 5 weeks

• Side Effect Profile of Topotecan

  Review of adverse events

  Up to 5 weeks

Secondary Outcomes (1)

• Response Rate

  Up to 12 weeks

Study Arms (1)

Dose Escalation and Radiation, Followed by Surgery

EXPERIMENTAL

Preoperative treatment with radiation and oral topotecan for up to 5 weeks, followed by surgery.

Drug: topotecan; Procedure: radiation; Procedure: surgery

Interventions

topotecan DRUG

Preoperative treatment: oral topotecan 5 days per week for up to 5 weeks

Dose Escalation and Radiation, Followed by Surgery

radiation PROCEDURE

Preoperative radiation

Dose Escalation and Radiation, Followed by Surgery

surgery PROCEDURE

surgery to remove tumor 4 to 8 weeks following completion of preoperative treatment

Dose Escalation and Radiation, Followed by Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed rectal cancer.
• Written Informed Consent
• Patients should be a candidate for preoperative radiotherapy
• A primary tumor of 3cm or greater with a clinical stage of T2, T3 or T4 and any N according to the Astler-Coller modification of the Dukes staging system
• Patient must be 18 years of age or older
• Must have an ECOG performance status of 2 or Less
• Diagnosis of rectal cancer should be no more than 90 days from initial clinic visit or from the start of therapy
• Patients must be seen and evaluated at the H. Lee Moffitt Cancer Center
• Patients must be recovered from prior surgery
• Patients must have a life expectancy of 3 months or greater
• Laboratory criteria: WBC of 3,500/mm3 or greater; Neutrophils of 1,500mm3 or greater; Platelet count of 100,000/mm3 or greater; Serum creatinine of 1.5 mg/dl or lesser; or creatinine clearance of greater than 60ml/min; SGOT/AST \& SGPT/ALT \& alkaline phosphatase of 2 times or lesser than the upper limit or normal if liver metastases are present; Serum bilirubin of 1.5mg/dl or lesser.

You may not qualify if:

• Patients with their primary tumor totally excised at time of diagnosis
• Patients with recurrent rectal cancer that failed initial treatment
• Patients previously treated with topotecan
• Patients with active infection
• Any known primary or secondary immunodeficiencies
• Any condition of the GI tract which would affect GI absorption or motility (e.g., autonomic neuropathy, active gastric or duodenal ulcers or certain gastrointestinal surgeries). Patients receiving medication to maintain motility or gastric emptying are also excluded.
• Patients with uncontrolled emesis, regardless of etiology.
• Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or a low grade prostate cancer.
• Concurrent severe medical problems unrelated to the malignancy which would significantly limit full compliance with the study or expose the patient to significant risk.
• Patients of child bearing potential, not practicing adequate contraception (barrier method or IUD for three months before the start of the study an agree to continue for at least 4 weeks after the end of the study)
• Patients who are pregnant or lactating
• Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Topotecan; Radiation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Physical Phenomena

Study Officials

• William Dinwoodie, MD

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2005
• First Posted: September 22, 2005
• Study Start: November 1, 2001
• Primary Completion: January 1, 2008
• Study Completion: January 1, 2008
• Last Updated: December 23, 2013

Record last verified: 2009-01

Locations

US (1)