Tirapazamine, Cisplatin, and Radiation Therapy in Treating Patients With Stage IB, Stage II, Stage III, or Stage IVA Cervical Cancer
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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 | Intervention | Phase |
|---|---|---|
|
Cervical Cancer |
Drug: cisplatin Drug: tirapazamine Radiation: brachytherapy Radiation: radiation therapy |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | 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 |
- Maximum tolerated dose of tirapazamine [ Designated as safety issue: Yes ]
- Safety and tolerability [ Designated as safety issue: Yes ]
- Failure-free survival [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Patterns of failure for the site of first failure (local-regional, distant, or both) [ Designated as safety issue: No ]
- Complete response rate at 12 weeks following study completion [ Designated as safety issue: No ]
- 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 [ Designated as safety issue: No ]
| Estimated Enrollment: | 22 |
| Study Start Date: | December 2004 |
| Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
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.
Eligibility| Genders Eligible for Study: | Female |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations| Australia, Victoria | |
| Peter MacCallum Cancer Centre | |
| East Melbourne, Victoria, Australia, 8006 | |
| Canada, Ontario | |
| Princess Margaret Hospital | |
| Toronto, Ontario, Canada, M5G 2M9 | |
| Study Chair: | Danny Rischin, MD | Peter MacCallum Cancer Centre, Australia |
More Information
No publications provided
| ClinicalTrials.gov Identifier: | NCT00098995 History of Changes |
| Other Study ID Numbers: | CDR0000393978, PMCC-2004/354, NCI-5485 |
| Study First Received: | December 8, 2004 |
| Last Updated: | January 15, 2010 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by National Cancer Institute (NCI):
|
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 |
Additional relevant MeSH terms:
|
Uterine Cervical Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Cervical Diseases Uterine Diseases |
Genital Diseases, Female Tirapazamine Cisplatin Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on May 19, 2013