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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00215956
First received: September 19, 2005
Last updated: December 20, 2013
Last verified: January 2009
  Purpose

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.


Condition Intervention Phase
Rectal Neoplasms
Drug: topotecan
Procedure: radiation
Procedure: surgery
Phase 1

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • Response Rate [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    To determine pathologic response to treatment and assessment of sphincter preservation.


Enrollment: 31
Study Start Date: November 2001
Study Completion Date: January 2008
Primary Completion Date: January 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose Escalation and Radiation, Followed by Surgery
Preoperative treatment with radiation and oral topotecan for up to 5 weeks, followed by surgery.
Drug: topotecan
Preoperative treatment: oral topotecan 5 days per week for up to 5 weeks
Procedure: radiation
Preoperative radiation
Procedure: surgery
surgery to remove tumor 4 to 8 weeks following completion of preoperative treatment

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00215956

Locations
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
GlaxoSmithKline
Investigators
Principal Investigator: William Dinwoodie, MD H. Lee Moffitt Cancer Center and Research Institute
  More Information

No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00215956     History of Changes
Other Study ID Numbers: MCC-12349, USFIRB#5881
Study First Received: September 19, 2005
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Topotecan
Rectal Neoplasms
Radiosensitizing

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Rectal Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Radiation-Sensitizing Agents
Topotecan
Physiological Effects of Drugs
Pharmacologic Actions
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014