Cisplatin and Radiation Therapy With or Without Tirapazamine in Treating Patients With Cervical Cancer - Full Text View

Sponsors and Collaborators:	Gynecologic Oncology Group National Cancer Institute (NCI) National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00262821

Purpose

RATIONALE: 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.

PURPOSE: 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.

Condition	Intervention	Phase
Cervical Cancer	Drug: cisplatin Drug: tirapazamine	Phase III

MedlinePlus related topics: Cancer

Drug Information available for: Cisplatin Tirapazamine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Active Control
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Progression-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Local control [ Designated as safety issue: No ]

Estimated Enrollment:	750
Study Start Date:	February 2006
Estimated Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: Active Comparator Patients receive cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6).	Drug: cisplatin Given IV
Arm II: Experimental 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.	Drug: cisplatin Given IV Drug: tirapazamine Given IV

Detailed Description:

OBJECTIVES:

Primary

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

Compare overall survival of patients treated with these regimens.
Compare the toxicity of these regimens in these patients.

Tertiary

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.
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.
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.
Correlate various combinations of biological markers of hypoxia and angiogenesis with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.
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: **Not required for patients with stage IB or IIA disease.

After completion of study treatment, patients are followed for at least 5 years.

PROJECTED ACCRUAL: A total of 750 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous cell carcinoma of the uterine cervix
- Stage IB2, IIA, IIB, IIIB, or IVA disease
  - Stage IIA tumors must be > 4 cm
- Primary, untreated disease
Negative, non-suspicious para-aortic nodes by lymphangiogram, CT scan, MRI, or lymphadenectomy
Must have been adequately clinically staged
Suitable for treatment with radical intent using concurrent chemotherapy and pelvic radiotherapy
No disease involvement of the lower third of the vagina regardless of stage (all stage IIIA, IIIB and IVA with lower one-third involvement)
No carcinoma of the cervical stump

PATIENT CHARACTERISTICS:

Performance status

GOG 0-3

Life expectancy

Not specified

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3

Hepatic

Bilirubin ≤ 1.5 times upper limit of normal (ULN)
SGOT ≤ 3 times ULN
Alkaline phosphatase ≤ 3 times ULN

Renal

Creatinine ≤ ULN or calculated creatinine clearance ≥ 60mL/min

Cardiovascular

No New York Heart Association class III-IV heart failure
No history of myocardial infarction
No unstable angina
No uncontrolled hypertension

Other

No pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No septicemia or severe infection
No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

PRIOR CONCURRENT THERAPY:

Surgery

No prior hysterectomy or planned hysterectomy as part of initial cervix cancer therapy
No prior coronary artery bypass surgery

Other

No prior cancer therapy that would preclude study treatment
No concurrent angina medication

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262821

Show 263 Study Locations

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

National Cancer Institute of Canada

Investigators

Study Chair:	Paul A. DiSilvestro, MD	Women and Infants Hospital of Rhode Island
Investigator:	Bradley J. Monk, MD	Chao Family Comprehensive Cancer Center
Study Chair:	Peter S. Craighead, MD	Tom Baker Cancer Centre - Calgary

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000455555, GOG-0219, CAN-NCIC-GOG-0219
Study First Received:	December 6, 2005
Last Updated:	January 15, 2009
ClinicalTrials.gov Identifier:	NCT00262821
Health Authority:	Unspecified

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

Study placed in the following topic categories:

Epidermoid carcinoma
Cisplatin
Squamous cell carcinoma
Carcinoma, squamous cell
Tirapazamine

Adenocarcinoma
Carcinoma, Squamous Cell
Carcinoma, Adenosquamous
Carcinoma

Additional relevant MeSH terms:

Radiation-Sensitizing Agents
Antineoplastic Agents
Therapeutic Uses
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009