A Phase I Study Of Tirapazamine In Combination With Radiation And Weekly Cisplatin In Patients With Locally Advanced Cervical Cancer
N/A
N/A
Female
Cervical Cancer
Trial Information
A Phase I Study Of Tirapazamine In Combination With Radiation And Weekly Cisplatin In Patients With Locally Advanced Cervical Cancer
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.
Inclusion 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 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of tirapazamine
Safety Issue:
Yes
Principal Investigator
Danny Rischin, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Peter MacCallum Cancer Centre, Australia
Authority:
United States: Food and Drug Administration
Study ID:
PMCC-2004/354
NCT ID:
NCT00098995
Start Date:
December 2004
Completion Date:
January 2010
Related Keywords:
- Cervical Cancer
- stage IB cervical cancer
- stage IIA cervical cancer
- stage IIB cervical cancer
- stage III cervical cancer
- stage IVA cervical cancer
- cervical adenocarcinoma
- cervical adenosquamous cell carcinoma
- cervical squamous cell carcinoma
- Uterine Cervical Neoplasms
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