Tirapazamine, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer

June 25, 2013 updated by: Peter MacCallum Cancer Centre, Australia

A Phase I Study Of Tirapazamine In Combination With Radiation And Weekly Cisplatin In Patients With Locally Advanced Cervical Cancer

RATIONALE: Drugs used in chemotherapy, such as tirapazamine and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Tirapazamine may help cisplatin kill more tumor cells by making tumor cells more sensitive to the drug. Radiation therapy uses high-energy x-rays to kill tumor cells. Tirapazamine may also make tumor cells more sensitive to radiation therapy. Giving radiation therapy in different ways together with combination chemotherapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of tirapazamine when given together with cisplatin and radiation therapy in treating patients with stage IB, stage II, stage III, or stage IVA cervical cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose and the recommended phase II and III dose of tirapazamine when combined with cisplatin and radiotherapy in patients with Stage IB-IVA squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix.
  • Determine the safety and tolerability of this regimen in these patients.

Secondary

  • Determine failure-free survival of patients treated with this regimen.
  • Determine overall survival of patients treated with this regimen.
  • Determine time to locoregional failure in patients treated with this regimen.
  • Determine patterns of failure for the site of first failure in patients treated with this regimen.
  • Determine the 12-week post-treatment complete response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of tirapazamine.

Patients receive tirapazamine IV over 2 hours on day 1 of weeks 1-5 and on days 3 and 5 of weeks 1 and 2 (cohort 2 only), OR days 3 and 5 of weeks 1-4 (cohort 3 only). Patients also receive cisplatin IV over 1 hour on day 1 of weeks 1-6. Patients concurrently undergo external beam radiotherapy once daily on days 1-5 for 5-5.5 weeks. After completion of chemoradiotherapy, patients undergo low-dose brachytherapy (up to 2 implants within an 8-week period) OR high-dose brachytherapy twice weekly for 5 treatments. Treatment continues in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of tirapazamine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. At least 10 patients are treated at the MTD.

Patients are followed at 2, 4, and 8 weeks, at 3 and 6 months, every 3 months for 2 years, and then every 6 months for 2 years.

PROJECTED ACCRUAL: A total of 3-22 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Anticipated)

22

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • East Melbourne, Victoria, Australia, 8006
        • Peter MacCallum Cancer Centre
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the cervix

    • Stage IB, IIA, IIB, III, or IVA disease

  • No evidence of involvement of para-aortic nodes by CT scan, MRI, fluorodeoxyglucose positron emission tomography, or lymphadenectomy

    • Involvement of common iliac nodes allowed
  • No evidence of distant metastases

PATIENT CHARACTERISTICS:

Age

  • Any age

Performance status

  • ECOG 0-2

Life expectancy

  • More than 6 months

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3

Hepatic

  • Bilirubin < 1.25 times upper limit of normal (ULN)
  • AST and ALT ≤ 3 times ULN

Renal

  • Calculated creatinine clearance ≥ 60 mL/min OR
  • Glomerular filtration rate ≥ 60 mL/min

Cardiovascular

  • No significant cardiac disease that would preclude IV fluid load required for administration of cisplatin
  • No symptomatic congestive heart failure
  • No unstable angina pectoris
  • No cardiac arrhythmia

Other

  • No symptomatic peripheral neuropathy ≥ grade 2

  • No clinically significant sensori-neural hearing impairment interfering with activities of daily living or requiring a hearing aid

    • Audiometric changes alone of any severity allowed
  • No history of allergic reaction attributed to compounds of similar chemical or biological composition to tirapazamine or cisplatin
  • No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
  • No ongoing or active infection
  • No psychiatric illness or social situation that would preclude study compliance
  • No other concurrent uncontrolled illness
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent epoetin alfa
  • No concurrent prophylactic filgrastim (G-CSF) or sargramostim (GM-CSF)
  • No concurrent pegfilgrastim

Chemotherapy

  • No prior chemotherapy for another malignancy

Endocrine therapy

  • Not specified

Radiotherapy

  • No prior pelvic or abdominal radiotherapy for another malignancy
  • No prior radiotherapy to ≥ 15% of bone marrow-bearing areas
  • No concurrent intensity-modulated radiotherapy
  • No concurrent interstitial brachytherapy

Surgery

  • Not specified

Other

  • No prior treatment for invasive cervical cancer
  • No other concurrent therapeutic investigational agents
  • No other concurrent anticancer therapy
  • No concurrent systemic retinoids
  • No concurrent amifostine
  • No concurrent combination antiretroviral therapy for HIV-positive patients

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety and tolerability
Maximum tolerated dose of tirapazamine

Secondary Outcome Measures

Outcome Measure
Overall survival
Failure-free survival
Patterns of failure for the site of first failure (local-regional, distant, or both)
Complete response rate at 12 weeks following study completion
Hypoxia by 18F-azomycinarabinoside (FAZA) PET scan at baseline and 12 wks following completion of radiotherapy correlated w/ obj. tumor response by PET- fludeoxyglucose F 18 (FDG) and local-regional failure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Peter MacCallum Cancer Centre, Australia

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Danny Rischin, MD, Peter MacCallum Cancer Centre, Australia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2004

Primary Completion (Actual)

January 1, 2010

Study Completion (Actual)

January 1, 2010

Study Registration Dates

First Submitted

December 8, 2004

First Submitted That Met QC Criteria

December 8, 2004

First Posted (Estimate)

December 9, 2004

Study Record Updates

Last Update Posted (Estimate)

June 26, 2013

Last Update Submitted That Met QC Criteria

June 25, 2013

Last Verified

November 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PMCC-2004/354
  • CDR0000393978 (Registry Identifier: PDQ (Physician Data Query))
  • NCI-5485

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Cervical Cancer

Clinical Trials on radiation therapy

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Canada

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe