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

This study has been completed.
Sponsor:
Collaborator:
NCIC Clinical Trials Group
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00262821
First received: December 6, 2005
Last updated: June 18, 2014
Last verified: June 2014

December 6, 2005
June 18, 2014
February 2006
August 2010   (final data collection date for primary outcome measure)
  • Progression-free survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Frequency and severity of adverse events assessed by Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
Not Provided
Complete list of historical versions of study NCT00262821 on ClinicalTrials.gov Archive Site
Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    Given IV
    Other Names:
    • CACP
    • CDDP
    • CPDD
    • DDP
  • Drug: tirapazamine
    Given IV
    Other Names:
    • SR 4233
    • Tirazone
    • WIN 59075
  • Active Comparator: Arm I (cisplatin)
    Patients receive cisplatin IV on days 1, 8, 15, 22, 29, and 36 (weeks 1-6).
    Intervention: Drug: cisplatin
  • 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.
    Interventions:
    • Drug: cisplatin
    • Drug: tirapazamine
DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a Gynecologic Oncology Group study. J Clin Oncol. 2014 Feb 10;32(5):458-64. doi: 10.1200/JCO.2013.51.4265. Epub 2014 Jan 6.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
402
Not Provided
August 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
  • Performance status - GOG 0-3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • SGOT ≤ 3 times ULN
  • Alkaline phosphatase ≤ 3 times ULN
  • Creatinine ≤ ULN or calculated creatinine clearance ≥ 60mL/min
  • No New York Heart Association class III-IV heart failure
  • No history of myocardial infarction
  • No unstable angina
  • No uncontrolled hypertension
  • 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
  • No prior hysterectomy or planned hysterectomy as part of initial cervix cancer therapy
  • No prior coronary artery bypass surgery
  • No prior cancer therapy that would preclude study treatment
  • No concurrent angina medication
  • No concurrent intensity-modulated radiotherapy
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00262821
NCI-2009-00591, NCI-2009-00591, CAN-NCIC-GOG-0219, CDR0000455555, GOG-0219, GOG-0219, U10CA027469
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
NCIC Clinical Trials Group
Principal Investigator: Paul DiSilvestro Gynecologic Oncology Group
National Cancer Institute (NCI)
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP