Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer
|Cervical Adenocarcinoma Cervical Adenosquamous Cell Carcinoma Cervical Squamous Cell Carcinoma Stage IB Cervical Cancer Stage IIA Cervical Cancer Stage IIB Cervical Cancer Stage III Cervical Cancer Stage IVA Cervical Cancer||Drug: cisplatin Drug: tirapazamine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||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|
- Progression-free Survival - Percentage of Patients Alive and Progression Free [ Time Frame: From study entry until first disease progression, death or date of last contact, up to 6 years ]Patients' progression status based on clinical, radiological or pathological (histological) evidence of disease after study therapy. Progression includes any death without evidence of disease progression. Progression-free Survival (PFS) is defined as time in month from study enrollment to disease progression, death or date of last contact.
- Overall Survival [ Time Frame: From study entry to death or last contact, up to 6 years ]The observed length of life from entry into the study to death or date of last contact.
- Adverse Events (Grade 3 or Higher) During Treatment Period [ Time Frame: All Adverse Events (AEs) occuring during treatment and up to 30 days after stopping the study treatment are reported ]Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v3.0.
|Study Start Date:||February 2006|
|Study Completion Date:||August 2010|
|Primary Completion Date:||August 2010 (Final data collection date for primary outcome measure)|
Active Comparator: Arm I (cisplatin)
Patients receive cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6).
Experimental: Arm II (cisplatin, tirapazamine)
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.
Other Names:Drug: tirapazamine
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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.
I. Compare overall survival of patients treated with these regimens. II. Compare the toxicity of these regimens in these patients.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00262821
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|Principal Investigator:||Paul DiSilvestro||Gynecologic Oncology Group|