Trials / Terminated

TerminatedNCT00262821

Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer

A Phase III, Randomized Trial of Weekly Cisplatin and Radiation Versus Cisplatin and Tirapazamine and Radiation in Stage IB2, IIA, IIIB and IVA Cervical Carcinoma Limited to the Pelvis

Status: Terminated
Phase: Phase 3
Study type: Interventional
Enrollment: 402 (actual)

Sponsor: National Cancer Institute (NCI) · NIH
Sex: Female
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This randomized phase III trial is studying cisplatin, radiation therapy, and tirapazamine to see how well they work compared to cisplatin and radiation therapy in treating patients with cervical cancer. Drugs used in chemotherapy, such as cisplatin and tirapazamine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin and tirapazamine may make tumor cells more sensitive to radiation therapy. It is not yet known whether giving cisplatin together with radiation therapy is more effective with or without tirapazamine in treating cervical cancer.

Detailed description

PRIMARY OBJECTIVE: I. Compare the progression-free survival of patients with stage IB, IIA, IIB, IIIB, or IVA carcinoma of the cervix treated with cisplatin and radiotherapy with vs without tirapazamine. SECONDARY OBJECTIVES: I. Compare overall survival of patients treated with these regimens. II. Compare the toxicity of these regimens in these patients. TERTIARY OBJECTIVES: I. Correlate study treatment with tumor expression of carbonic anhydrase IX (CA-IX) and recurrence-free survival, overall survival, or metastasis in patients treated with these regimens. II. Correlate expression of CA-IX, hypoxia inducible factor-1α, CD-31, thrombospondin-1, CD-105, or vascular endothelial growth factor (VEGF) in primary tumor tissue with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens. III. Correlate pre-treatment and/or post-treatment serum concentrations of angiogenic markers including angiogenin or VEGF with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens. IV. Correlate various combinations of biological markers of hypoxia and angiogenesis with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens. V. Correlate levels of individual biological markers of hypoxia or angiogenesis with clinicopathological characteristics including tumor size, histologic subtype, FIGO stage, depth of invasion, pelvic node status, site of recurrence, and hemoglobin level as well as patient, age, race and performance status in patients treated with these regimens. OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to FIGO stage of disease (IB2 vs IIA vs IIB vs IIIB vs IVA), brachytherapy method (low-dose rate vs high-dose rate), surgical staging of para-aortic nodes (yes vs no). Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive cisplatin IV over 30-60 minutes once weekly on days 1, 8, 15, 22, 29, and 36 (weeks 1-6). Patients also undergo external beam radiotherapy to the pelvis once daily on days 1-5, 8-12, 15-19, 22-26, and 29-33 (weeks 1-5). Patients then receive either 1 or 2 applications of low-dose rate brachytherapy in weeks 6-8 OR 5 applications of high-dose rate (HDR)\* brachytherapy once weekly in weeks 4-8 and 3-5 days of parametrial boost radiotherapy\*\* beginning after the first brachytherapy implant. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive tirapazamine IV over 2 hours on days 1, 8, 10, 12, 15, 22, 24, 26, and 29 and cisplatin IV over 1 hour on days 1, 15, and 29. Patients also undergo radiotherapy and brachytherapy as in arm I. Treatment continues in the absence of disease progression or unacceptable toxicity. NOTE: \*No external beam radiotherapy is administered on the day of HDR brachytherapy. If the majority of external beam radiotherapy has been administered, HDR brachytherapy may be administered in 2 applications per week (separated by at least 72 hours) in order to complete all treatment within 8 weeks. NOTE: \*\* Patients may receive a parametrial boost at the discretion of the treating radiation oncologist. After completion of study treatment, patients are followed for at least 5 years.

Conditions

Interventions

Type	Name	Description
DRUG	cisplatin	Given IV
DRUG	tirapazamine	Given IV

Timeline

Start date: 2006-02-01
Primary completion: 2010-08-01
Completion: 2010-08-01
First posted: 2005-12-07
Last updated: 2019-07-23
Results posted: 2017-07-02

Locations

282 sites across 2 countries: United States, Canada

Source: ClinicalTrials.gov record NCT00262821. Inclusion in this directory is not an endorsement.