Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

• Status: Not yet recruiting
• Trial end date: 2029-04-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborators: Calithera Biosciences, Inc; National Cancer Institute (NCI)
• Treatments: Cisplatin

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.

• Creatinine clearance ≤ 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.

• 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)