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

Sponsor

Peter MacCallum Cancer Centre, Australia (Other)

Overall Status

Completed

CT.gov ID

NCT00098995

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
Cervical Cancer	Drug: cisplatin Drug: tirapazamine Radiation: brachytherapy Radiation: radiation therapy	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

22 participants

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2004

Actual Primary Completion Date :

Jan 1, 2010

Actual Study Completion Date :

Jan 1, 2010

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of tirapazamine []
Safety and tolerability []

Secondary Outcome Measures

Failure-free survival []
Overall 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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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