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

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ClinicalTrials.gov Identifier: NCT00215956
Recruitment Status : Completed
First Posted : September 22, 2005
Last Update Posted : December 23, 2013
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute

Tracking Information
First Submitted Date  ICMJE September 19, 2005
First Posted Date  ICMJE September 22, 2005
Last Update Posted Date December 23, 2013
Study Start Date  ICMJE November 2001
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
  • Maximum Tolerated Dose (MTD) of Topotecan [ Time Frame: up to 5 weeks ]
    Dose escalation to determine MTD that can be given with radiation.
  • Side Effect Profile of Topotecan [ Time Frame: Up to 5 weeks ]
    Review of adverse events
Original Primary Outcome Measures  ICMJE
 (submitted: September 19, 2005)
  • Maximum Tolerated Dose of topotecan
  • Side Effect Profile of Topotecan
Change History Complete list of historical versions of study NCT00215956 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2013)
Response Rate [ Time Frame: Up to 12 weeks ]
To determine pathologic response to treatment and assessment of sphincter preservation.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2005)
Response Rate
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma
Official Title  ICMJE A Phase I Study of Oral Topotecan as a Radiosensitizing Agent in Patients With Rectal Carcinoma
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Rectal Neoplasms
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Dose Escalation and Radiation, Followed by Surgery
Preoperative treatment with radiation and oral topotecan for up to 5 weeks, followed by surgery.
Interventions:
  • Drug: topotecan
  • Procedure: radiation
  • Procedure: surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2013)
31
Original Enrollment  ICMJE
 (submitted: September 19, 2005)
28
Actual Study Completion Date  ICMJE January 2008
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00215956
Other Study ID Numbers  ICMJE MCC-12349
USFIRB#5881
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party H. Lee Moffitt Cancer Center and Research Institute
Study Sponsor  ICMJE H. Lee Moffitt Cancer Center and Research Institute
Collaborators  ICMJE GlaxoSmithKline
Investigators  ICMJE
Principal Investigator: William Dinwoodie, MD H. Lee Moffitt Cancer Center and Research Institute
PRS Account H. Lee Moffitt Cancer Center and Research Institute
Verification Date January 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP