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

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Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, Treatment18 and overGOG-0219
NCI-2009-00591, CAN-NCIC-GOG-0219, CDR0000455555, NCT00262821

Trial Description

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.

Further Study Information

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.

Eligibility Criteria

Inclusion Criteria:

No other invasive malignancy within the past 5 years except nonmelanoma skin cancer

No concurrent intensity-modulated radiotherapy

Negative pregnancy test

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 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

No disease involvement of the lower third of the vagina regardless of stage (all stage IIIA, IIIB and IVA with lower one-third involvement)

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

Fertile patients must use effective contraception

No septicemia or severe infection

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

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
  • NCIC-Clinical Trials Group
Paul A. DiSilvestro, Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00262821

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.