Neoadjuvant Bevacizumab and Carboplatin Followed by Concurrent Bevacizumab, Carboplatin and Radiotherapy in the Primary Treatment of Cervix Cancer

Inclusion Criteria:

* Patients must have IB2 and IIA tumors greater than 4 cm in diameter, IIB, IIIB without hydronephrosis or non-functioning kidney, and IVA without invasion to the bladder or rectum, primary, previously untreated, and histologically confirmed invasive squamous cell carcinoma, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix.
* Negative, non-suspicious para-aortic nodes determined by CT lymphangiogram, MRI or lymphadenectomy.
* Adequate bone marrow function: ANC greater ≥ 1,500/mm3, platelets ≥ 100,000/mm3.
* Adequate renal function: serum creatinine ≤ 1.5 mg/100 mL.
* Adequate hepatic function: bilirubin less than or equal to 1.5 x upper limit of normal (ULN) and SGOT and alkaline phosphatase less than or equal to 3 x ULN.
* Zubrod Performance Status of 0 or 1
* Patients of childbearing potential must have a negative serum pregnancy test within14 days of enrolling in this study and use an effective form of contraception during the study period.
* Patients who are medically suitable for treatment with radical intent using concurrent chemotherapy and pelvic radiation.

Exclusion Criteria:

* Patients with Stage IA, IB1, IB2 and IIa tumors less than 4 cm in diameter, IIIA or IVB disease.
* Patients who have known metastases to para-aortic or scalene nodes or metastases to other organs outside the radiation field at the time of the original clinical and surgical staging.
* Extensive tumor preventing intracavitary irradiation.
* Distal vaginal involvement or any disease such that an interstitial implant might be necessary
* Previous pelvic or abdominal radiation, cytotoxic chemotherapy, or previous therapy of any kind for this malignancy.
* Patients who might require an emergency surgical procedure to relieve hydronephrosis, or who are at risk of perforating the bladder and might require surgery.
* Patients with renal abnormalities, such as pelvic kidney, horseshoe kidney, or renal transplantation, that would require modification of radiation fields
* Life expectancy of less than 12 weeks
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study.
* Septicemia or severe infection
* Patients who have circumstances that will not permit completion of this study or the required follow-up.
* Patients who are pregnant at the time of diagnosis and do not wish pregnancy termination prior to initiation of treatment.
* Other concomitant malignancies, with the exception of nonmelanoma skin cancer, who had (or have) any evidence of other cancer present within the last 5 years.
* Bevacizumab-Specific Exclusions
* Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)
* Any prior history of hypertensive crisis or hypertensive encephalopathy
* New York Heart Association (NYHA) Grade II or greater congestive heart failure
* Known CNS disease
* Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
* Symptomatic peripheral vascular disease
* Evidence of bleeding diathesis or coagulopathy
* Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
* Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
* History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
* Serious, non-healing wound, ulcer, or bone fracture
* Proteinuria at screening as demonstrated by either
* Urine protein:creatinine (UPC) ratio ≥1.0 at screening OR
* Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
* Known hypersensitivity to any component of bevacizumab
* Pregnant (positive pregnancy test) or lactating. Use of effective means of contraception (men and women) in subjects of child-bearing potential
* Any history of stroke or transient ischemic attack at any time
* History of myocardial infarction or unstable angina within 6 months of study enrollment
* Carboplatin-Specific Exclusions
* History of severe allergic reactions to cisplatin or other platinum-containing compounds.
* Patients with severe bone marrow depression or significant bleeding.