glutaminase inhibition and chemoradiation in advanced cervical cancer

Conditions: Advanced Cervical Carcinoma; Cervical Cancer; Cervix Cancer; Cancer of the Cervix

Summary: advanced cervical cancer patients treated with standard of care (soc) chemoradiation plus glutaminase inhibition with telaglenastat (cb-839) will have increased progression-free survival (pfs) compared to historical rates for patients receiving soc chemoradiation alone.


Eligibility criteria:
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)

Keywords: advanced cervical cancer glutaminase inhibitor