Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

Launched by WASHINGTON UNIVERSITY SCHOOL OF MEDICINE · Aug 26, 2022

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ClinConnect Summary

This clinical trial is looking at a new treatment approach for patients with advanced cervical cancer. Researchers want to see if combining standard treatment (chemoradiation) with a drug called telaglenastat (CB-839), which works by blocking a specific enzyme, can help patients live longer without their cancer getting worse. They hope that this combination will improve the time patients can go without progression of their disease compared to those receiving standard treatment alone.

To be eligible for the trial, participants must be at least 18 years old and have been newly diagnosed with advanced cervical cancer. They should be able to receive the standard chemoradiation treatment and have certain health markers within a specific range. This includes having a good overall health status, normal blood counts, and no uncontrolled health issues. If someone joins the trial, they can expect to receive the combination treatment and will be monitored closely by the medical team. It’s important to know that the trial is not yet recruiting participants, so they will have to wait for it to begin before applying.

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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)