Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

Phase II Study of Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cervical Cancer; Cervix Cancer; Advanced Cervical Carcinoma; Cancer of the Cervix
• Intervention / Treatment: Radiation: Radiation treatment; Drug: Cisplatin; Drug: Telaglenastat

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Julie K Schwarz, M.D., Ph.D.; Phone Number: 314-608-6813; Email: jschwarz@wustl.edu

Study Locations

• United States
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
      • Sub-Investigator: Esther Lu, Ph.D.
      • Sub-Investigator: David DeNardo, Ph.D.
      • Sub-Investigator: Stephanie Markovina, M.D., Ph.D.
      • Sub-Investigator: Matthew Powell, M.D.
      • Sub-Investigator: Lindsay Kuroki, M.D.
      • Sub-Investigator: L. Stewart Massad, M.D.
      • Sub-Investigator: Carolyn McCourt, M.D.
      • Sub-Investigator: David Mutch, M.D.
      • Sub-Investigator: Premal Thaker, M.D.
      • Sub-Investigator: Dineo Khabele, M.D.
      • Contact: Julie K Schwarz, M.D., Ph.D.; Phone Number: 314-608-6813; Email: jschwarz@wustl.edu
      • Principal Investigator: Julie K Schwarz, M.D., Ph.D.
      • Sub-Investigator: Andrea Hagemann, M.D., MSCI
      • Sub-Investigator: Maggie Mullen, M.S.
      • Sub-Investigator: Gary Patti, Ph.D.
      • Sub-Investigator: Li Ding, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control Arm: Standard of Care Chemoradiation; -Participants will receive 7 weeks of standard of care chemoradiation.	Radiation: Radiation treatment; Standard of care; External beam radiation therapy delivered daily 4 days a week and 1 day per week of brachytherapy.; Drug: Cisplatin; Standard of care; Weekly administration of cisplain
Experimental: 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.	Radiation: Radiation treatment; Standard of care; External beam radiation therapy delivered daily 4 days a week and 1 day per week of brachytherapy.; Drug: Cisplatin; Standard of care; Weekly administration of cisplain; Drug: Telaglenastat; -800 mg twice per day by mouth; Other Names: CB-893

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS) - experimental arm only	PFS is defined as the duration of time from start of telaglenastat to time of progression or death, whichever occurs first.; Progressive disease: New foci of abnormal FDG uptake not present on the pretreatment FDG-PET study	Through completion of follow-up (estimated to be 24 months and 9 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity as measured by number of acute adverse events experienced by participant - experimental arm only	Toxicity evaluation will report events according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE); Acute toxicity is defined as any toxicity occurring within 90 days from first receiving study radiotherapy or death, whatever event is observed first.	From start of chemoradiation treatment through 90 days
Late toxicity as measured by number of late adverse events experienced by participant - experimental arm only	Toxicity evaluation will report events according to Common Terminology Criteria for Adverse Events v5.0 (CTCAE); Late toxicities include any toxicity that is determined possibly, probably, or definitely related to treatment, within 24 months after completion of treatment.	From day 91 through 24 months after completion of chemoradiation
Overall survival (OS)	-OS is defined as the days from the start of Telaglenastat treatment to the date of death, censored at the last follow-up otherwise.	Through completion of follow-up (estimated to be 24 months and 9 weeks)

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: National Cancer Institute (NCI); Calithera Biosciences, Inc
• Investigators: Principal Investigator: Julie K Schwarz, M.D., Ph.D., Washington University School of Medicine

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): October 7, 2032
• Study Completion (Estimated): October 7, 2032

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: August 26, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: advanced cervical cancer; Glutaminase Inhibitor
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Neoplasms; Uterine Cervical Neoplasms; Therapeutics; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Cisplatin; Radiotherapy
• Other Study ID Numbers: 202301163; R01CA181745 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No