Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

Inclusion Criteria:

Patients eligible for definitive chemoradiotherapy, including brachytherapy

* Patient age ≥ 18 years.
* Patients with histologically confirmed newly diagnosed advanced cervical cancer (squamous, adenosquamous, adenocarcinoma or poorly differentiated); Federation of Gynecology and Obstetrics (FIGO) 2018 clinical stages III-IVA.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Absolute neutrophil count ≥ 1,500/mcL.
* Platelets ≥ 100,000/mcL.
* Hemoglobin ≥ 8 g/dL (can be transfused prior to study).
* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); patients with known Gilbert disease with serum bilirubin ≤ 3 x ULN may be enrolled.
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]/alanine aminotransfersase (ALT) (serum glutamate pyruvate transaminase \[SGPT\] ≤ 2.5 x ULN.
* Alkaline phosphatase ≤ 2.5 x ULN.
* Serum creatinine ≤ 1.5 mg/dL to receive weekly cisplatin; patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin if there is no hydronephrosis and the estimated creatinine clearance (CCr) is ≥ 30 ml/min. For the purpose of estimating the CCr, formulas, including Cockcroft and Gault for females or similar, should be used.
* International normalize ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (this applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation, such as low-molecular weight heparin or warfarin, should be on a stable dose).
* Patient does not have uncontrolled diabetes mellitus (i.e. fasting blood glucose \>200 mg/dL).
* Patient does not have a known allergy to cisplatin or compounds of similar biologic composition as CB-839.
* Patient is not actively breastfeeding (or has agreed to discontinue before the initiation of protocol therapy).
* Ability to understand and the willingness to sign a written informed consent document.
* Patients does not have known human immunodeficiency virus syndrome (HIV testing optional).

Exclusion Criteria:

* Patient has another concurrent active invasive malignancy.
* Patient has received prior radiation therapy to the pelvis or previous therapy of any kind for this malignancy, or pelvic radiation for any prior malignancy.
* Patient is receiving another investigational agent for the treatment of cancer.
* Poorly controlled diabetes, with inability to perform 18F-FDG PET scan.
* Patient is pregnant or breastfeeding.
* Uncontrolled intercurrent illness 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.
* Mean resting QTc \> 470 msec obtained by electrocardiogram (ECG).
* Severe, active co-morbidity defined as follows:

  * Current (within 28 days of cycle 1, day 1) signs and/or symptoms of bowel obstruction
  * Patients who require parental hydration and/or nutrition
  * Patients who require drainage gastrostomy tube
  * Evidence of bleeding diathesis or clinically significant coagulopathy
  * Serious, non-healing or dehiscing wound, active ulcer or untreated bone fracture
  * History of hemoptysis (\>= 1/2 teaspoon of bright red blood per episode) within 1 month of study enrollment
  * Significant cardiovascular or cerebrovascular disease including: Uncontrolled hypertension (systolic blood pressure \[SBP\] \>= 150; diastolic blood pressure \[DBP\] \>= 90)