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

• r Primary tumor response rate at 4-6 weeks post treatment [ Time Frame: 3 months from start of therapy ] [ Designated as safety issue: No ]
• Disease-free survival assessed every 3-6 months [ Time Frame: 5 years ] [ Designated as safety issue: No ]
• Overall survival assessed every 3 months for 2 years and then every 6 months for 5 years [ Time Frame: 5 years ] [ Designated as safety issue: No ]

RATIONALE: Drugs used in chemotherapy, such as cisplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Hyperthermia therapy kills tumor cells by heating them to several degrees above body temperature. It is not yet known whether chemotherapy and radiation therapy are more effective with or without hyperthermia therapy in treating cervical cancer.

PURPOSE: This randomized phase III trial is studying how well giving cisplatin and radiation therapy together with hyperthermia therapy works compared to cisplatin and radiation therapy alone in treating patients with locally advanced cervical cancer.

OBJECTIVES:

• Compare local control, failure-free survival, and overall survival of patients with locally advanced carcinoma of the cervix treated with cisplatin and radiotherapy with vs without hyperthermia .

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, disease stage (IIB or IIIA vs IIIB or IVA) and age (< 60 years vs ≥ 60 years). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive cisplatin IV and concurrently undergo hyperthermia over 60-90 minutes on day 1. Patients also undergo external beam radiotherapy once daily on days 1-5. Treatment repeats weekly for 5-6 weeks in the absence of disease progression or unacceptable toxicity. After completion of chemoradiotherapy and hyperthermia, patients undergo brachytherapy to the cervix for 2-3 days.
• Arm II: Patients receive cisplatin and undergo radiotherapy (including brachytherapy) as in arm I.

Patients are followed at 4-6 weeks, every 3 months for 2 years, every 6 months for 5 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 400 patients (200 per treatment arm) will be accrued for this study within 5 years.

• Drug: cisplatin
  Given IV
  Other Name: Platinol-AQ
• Procedure: hyperthermia treatment
  Patients undergo hyperthermia treatment over 60-90 minutes
• Radiation: brachytherapy
  Patients undergo brachytherapy for 2-3 days
• Radiation: external beam radiation therapy
  Patients undergo external beam radiation therapy once daily on days 1-5

• Experimental: Arm I
  Patients receive cisplatin IV and concurrently undergo hyperthermia treatment over 60-90 minutes on day 1. Patients also undergo external beam radiation therapy once daily on days 1-5. Treatment repeats weekly for 5-6 weeks in the absence of disease progression or unacceptable toxicity. After completion of chemoradiotherapy and hyperthermia, patients undergo brachytherapy to the cervix for 2-3 days.
  Interventions:

  • Drug: cisplatin
  • Procedure: hyperthermia treatment
  • Radiation: brachytherapy
  • Radiation: external beam radiation therapy
• Active Comparator: Arm II
  Patients receive cisplatin and undergo external beam radiation therapy (and brachytherapy) as in arm I.
  Interventions:

  • Drug: cisplatin
  • Radiation: brachytherapy
  • Radiation: external beam radiation therapy

Inclusion criteria:

Invasive cervical carcinoma (squamous, adeno or adenosquamous histologies, small cell histology excluded)

• age >18years
• International Federation of Gynecology and Obstetrics ((FIGO) stage IB2, IIA-IVA, FIGO stages IA, IB1 with positive pelvic lymph nodes or parametria either on imaging techniques or pathologically involved at the time of surgery.

patients undergoing surgical removal of the cervix and uterus are not eligible, parametria either on imaging techniques or pathologically involved at the time • Performance status Eastern Cooperative Oncology Group(ECOG)/World Health Organisation (WHO) 0, 1 or >/=70%respectively White Blood count (WBC) ≥ 3,000, platelets ≥ 100,000, Absolute Neutrophil Count (ANC) > 1500

• serum bilirubin ≤ 1.5 times upper limit of normal, transaminase ≤ 3 times upper limit of normal calculated creatinine clearance >60milliliters (mls)/liter ( Cockcroft) OR creatinine </= 2.0mgs% paraaortic adenopathy absent or 1.5 centimeter (cm) in greatest dimension on Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) scan;

No history of myocardial infarction in the last 6 months no symptomatic angina pectoris negative pregnancy test in patients under 50 Hemoglobin >12.0 Gd/dl or >7.5 mmo;/L with transfusion if needed written written informed consent

Exclusion criteria:

surgical resection of the primary tumor (i.e. Total abdominal hysterectomy (TAH)/ Bilateral salpingoophorectomy (BSO)

• patients with pacemakers or implanted defibrillators
• patients with significant metallic foreign bodies (i.e. hip replacements, bone metallic rods,orthopedic plates, etc.)
• prior radiotherapy or chemotherapy