Bevacizumab, Radiation Therapy, and Cisplatin in Treating Patients With Previously Untreated Locally Advanced Cervical Cancer

This phase II trial is studying how well giving bevacizumab together with radiation therapy and cisplatin works in treating patients with previously untreated locally advanced cervical cancer. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of cervical cancer by blocking blood flow to the tumor. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with radiation therapy and cisplatin may kill more tumor cells.

PRIMARY OBJECTIVES:

I. Determine treatment-related serious adverse-event rates and adverse-event rates within the first 90 days from treatment start in patients with previously untreated locally advanced carcinoma of the cervix treated with bevacizumab, cisplatin, and concurrent pelvic radiotherapy.

SECONDARY OBJECTIVES:

I. Evaluate treatment-related serious adverse events and adverse events at any time.

II. Evaluate disease-free survival (local, regional, or distant failure, or death due to any cause).

III. Evaluate overall survival (death due to any cause). IV. Implement the image-based brachytherapy guidelines proposed by the Transatlantic Image-Guided Brachytherapy Working Group.

V. Collect CT scan or MRI-based dosimetry of brachytherapy applications used during the course of treatment for later analysis of feasibility and consistency as well as dose/volume assessments of tumor control and complications.

OUTLINE: This is a multicenter study.

Patients undergo pelvic external-beam radiotherapy (EBRT) once daily, 5 days a week, for 5 weeks for a total of 45 Gy.

Some patients also undergo low-dose rate brachytherapy twice, 1-3 weeks apart, beginning \>= 4 weeks after initiating EBRT or high-dose rate brachytherapy 5 times, \>= 48 hours apart, beginning \>= 2 weeks after initiating EBRT. EBRT and chemotherapy are halted on the day of high-dose rate brachytherapy. Patients receive bevacizumab IV over 30-90 minutes on days 1, 15, and 29 and cisplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 35.

After completion of study treatment, patients are followed periodically.

Eligibility Criteria:
Inclusion Criteria:

* Histologically confirmed squamous cell, adenocarcinoma, or adenosquamous cell carcinoma of the uterine cervix, meeting 1 of the following stage criteria:

  * Stage IIB-IIIB lymph nodes
  * Stage IB-IIA disease with biopsy-proven pelvic node metastases and/or tumor size \>= 5 cm
* No positive para-aortic lymph nodes
* Zubrod performance status 0-2
* WBC \>= 3,000/mm\^3
* Absolute granulocyte count \>= 1,500/mm\^3
* Platelet count \>= 100,000/mm\^3
* INR \< 1.5
* Total bilirubin =\< 1.5 mg/dL
* Serum creatinine =\< 1.5 mg/dL
* AST and ALT =\< 2.5 times upper limit of normal (ULN)
* Serum calcium =\< 1.3 times ULN
* Hemoglobin \>= 10 g/dL (transfusion allowed)
* Urine protein:creatinine ratio ? 0.5 OR urine protein \< 1,000 mg by 24-hour urine collection
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* None of the following illnesses or conditions:

  * Medical illness preventing the use of full-dose chemotherapy
  * Evidence of bleeding diathesis or coagulopathy
  * Prior medical or psychiatric illness that would prevent informed consent or limit survival to \< 6 months
  * History of aneurysms, cerebrovascular accident, or arteriovenous malformations
  * Active gastrointestinal (GI) ulcers, GI bleeding, or active inflammatory bowel disease
  * Serious, nonhealing wound, ulcer, or current healing fracture
  * History of any type of fistula or GI perforation
  * Intra-abdominal abscess within the past 6 months
* No prior invasive malignancy (except nonmelanomatous skin cancer) unless disease free for \>= 3 years
* No significant traumatic injury within the past 28 days
* No clinically significant cardiovascular disease, such as the following:

  * Uncontrolled hypertension (blood pressure \> 160/90 mm Hg on medication)
  * Myocardial infarction within the past 12 months
  * Unstable angina within the past 12 months
  * New York Heart Association class II-IV congestive heart failure
  * Unstable symptomatic arrhythmia requiring medication (i.e., chronic atrial arrhythmia, atrial fibrillation, or paroxysmal supraventricular tachycardia)
  * Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months
* Arterial thromboembolic events, including transient ischemic attack or clinically significant peripheral artery disease, within the past 6 months
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* No known HIV
* No prior organ transplant
* No prior surgery for carcinoma of the cervix other than biopsy
* No prior surgical debulking of pelvic or para-aortic nodes
* No prior pelvic radiotherapy, including transvaginal irradiation to control bleeding
* No prior systemic chemotherapy
* No major surgical procedure or open biopsy within the past 28 days or anticipation of need for major surgical procedure during the course of the study
* No fine needle aspirations or core biopsies within the past 7 days
* No concurrent major surgical procedure
* No concurrent epoetin alfa or Hypericum perforatum (St. John's wort)
* No concurrent intensity-modulated radiotherapy
* No concurrent transvaginal irradiation to control bleeding