This randomized phase III trial studies how well giving cisplatin and radiation therapy together with or without carboplatin and paclitaxel works in treating patients with cervical cancer has spread from where it started to nearby tissue or lymph nodes. Drugs used in chemotherapy, such as cisplatin, carboplatin, and paclitaxel, work in different ways to stop the growth of [cancer/tumor] cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. External 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. It is not yet known whether giving cisplatin and external and internal radiation therapy together with carboplatin and paclitaxel kills more tumor cells.

PRIMARY OBJECTIVES:

I. To determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves overall survival.

SECONDARY OBJECTIVES:

I. To determine the progression-free survival rates. II. To determine acute and long-term toxicities. III. To determine patterns of disease recurrence. IV. To determine the association between radiation protocol compliance and outcomes.

V. To determine patient quality of life, including psycho-sexual health.

TERTIARY OBJECTIVES:

I. To determine the association between the results of a follow-up positron emission tomography (PET) scan performed 4-6 months post completion of chemoradiation and outcomes for all patients in the trial.

II. To determine the biological predictors of patients' outcomes based on translational laboratory studies of blood and tissue specimens.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cisplatin intravenously (IV) over 60-90 minutes on days 1, 8, 15, 22, and 29. Patients also undergo external-beam radiation therapy once daily, 5 days a week, for approximately 5 weeks. Patients then undergo high-dose rate, pulsed-dose rate, or low-dose rate intracavitary brachytherapy.

ARM II: Patients receive cisplatin and undergo external-beam radiation and brachytherapy as in arm I. Beginning 4 weeks later, patients also receive adjuvant chemotherapy comprising paclitaxel IV over 3 hours and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo baseline tumor biopsy and blood collection for future correlative studies.

Patients complete the European Organization for Research and Treatment of Cancer (EORTC) Core questionnaire (QLQ-C30), the EORTC cervix cancer module (CX24), the ovarian cancer module (OV28), and the Sexual function-Vaginal Changes Questionnaire (SVQ) questionnaires at baseline, during, and after completion of study treatment.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Inclusion Criteria:

• Eligible patients will have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent, in addition to:

  • Federation of Gynecology and Obstetrics (FIGO) 2008 stage IB1 & node positive, IB2, IIA, IIB, IIIB, or IVA disease

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2

• Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix

• White blood cells (WBC) >= 3.0 x 10^9/L

• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

• Platelet count >= 100 x 10^9/L

• Bilirubin =< 1.5 times upper limit of normal (ULN)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN (if both tests are done, both results need to be =< 2.5 x ULN)

• Creatinine =< ULN (Common Toxicity Criteria [CTC] grade 0) OR calculated creatinine clearance (Cockcroft-Gault formula) >= 60 mL/min OR >= 50 mL/min by ethylenediaminetetraacetic acid (EDTA) creatinine clearance

• Written informed consent

Exclusion Criteria:

• Any previous pelvic radiotherapy
• Para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven, PET positive, or >= 15 mm short-axis diameter on computed tomography [CT])
• FIGO 2008 stage IIIA disease
• Patients assessed at presentation as requiring interstitial brachytherapy treatment
• Patients with bilateral hydronephrosis unless at least one side has been stented and renal function fulfills the required inclusion criteria
• Previous chemotherapy for this tumor
• Evidence of distant metastases
• Prior diagnosis of Crohn's disease or ulcerative colitis
• Peripheral neuropathy >= grade 2 (per Common Terminology Criteria for Adverse Events [CTCAE] version [v]4)
• Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy; this includes patients with a prior history of supracervical hysterectomy
• Patients with other invasive malignancies, with the exception of non-melanoma skin cancer and in situ melanoma, who had (or have) any evidence of the other cancer present within the last 5 years
• Patients who are pregnant or lactating
• Any contraindication to the use of cisplatin, carboplatin, or paclitaxel chemotherapy
• Serious illness or medical condition that precludes the safe administration of the trial treatment including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients who are known to be human immunodeficiency virus (HIV) positive