Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

NCT ID: NCT05521997

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2032-03-07

Brief 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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control Arm: Standard of Care Chemoradiation

-Participants will receive 7 weeks of standard of care chemoradiation.

Group Type: ACTIVE_COMPARATOR

Radiation treatment

Intervention Type: RADIATION

• Standard of care
• External beam radiation therapy delivered daily 4 days a week and 1 day per week of brachytherapy.

Cisplatin

Intervention Type: DRUG

• Standard of care
• Weekly administration of cisplain

Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation

-Participants will receive 2 weeks of telaglenastat and 7 weeks of standard of care chemoradiation plus telaglenastat.

Group Type: EXPERIMENTAL

Telaglenastat

Intervention Type: DRUG

-800 mg twice per day by mouth

Radiation treatment

Intervention Type: RADIATION

• Standard of care
• External beam radiation therapy delivered daily 4 days a week and 1 day per week of brachytherapy.

Cisplatin

Intervention Type: DRUG

• Standard of care
• Weekly administration of cisplain

Interventions

Telaglenastat

-800 mg twice per day by mouth

Intervention Type: DRUG

Radiation treatment

• Standard of care
• External beam radiation therapy delivered daily 4 days a week and 1 day per week of brachytherapy.

Intervention Type: RADIATION

Cisplatin

• Standard of care
• Weekly administration of cisplain

Intervention Type: DRUG

Other Intervention Names

CB-893

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie K Schwarz, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Central Contacts

Julie K Schwarz, M.D., Ph.D.

Role: CONTACT

jschwarz@wustl.edu

314-608-6813

Facility Contacts

Julie K Schwarz, M.D., Ph.D.

Role: primary

jschwarz@wustl.edu

314-608-6813

Related Links

http://www.siteman.wustl.edu

Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Other Identifiers

R01CA181745

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202301163

Identifier Type: -

Identifier Source: org_study_id