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

This study is currently recruiting patients.

Sponsors and Collaborators: Peter MacCallum Cancer Centre, Australia
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)

Purpose

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.

Condition Treatment or Intervention Phase
Cervical Cancer
 Drug: cisplatin
 Drug: tirapazamine
 Procedure: brachytherapy
 Procedure: chemosensitization/potentiation
 Procedure: chemotherapy
 Procedure: radiation therapy
 Procedure: radiosensitization
Phase I

MedlinePlus related topics:  Cervical Cancer

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Tirapazamine in Combination With Cisplatin and Radiotherapy in Patients With Stage IB-IVA Squamous Cell Carcinoma, Adenocarcinoma, or Adenosquamous Cell Carcinoma of the Cervix

Further Study Details: 

OBJECTIVES: Primary

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.

Eligibility

Genders Eligible for Study:  Both

Criteria

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 neuropathygrade 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

Chemotherapy

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


Location and Contact Information


Australia, Victoria
      Peter MacCallum Cancer Centre, East Melbourne,  Victoria,  3002,  Australia; Recruiting
Danny Rischin, MD  61-3-9656-1804 

Canada, Ontario
      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting
Anthony Fyles, MD  416-946-6522 

Study chairs or principal investigators

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

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000393978; PMCC-2004/354; NCI-5485; NCT00098995
Record last reviewed:  December 2004
Last Updated:  April 4, 2005
Record first received:  December 8, 2004
ClinicalTrials.gov Identifier:  NCT00098995
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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