Glutaminase Inhibition and Chemoradiation in Advanced Cervical Cancer

NCT05521997 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 202301163R01CA181745
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Keywords

advanced cervical cancer; Glutaminase Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Acute toxicity as measured by number of acute adverse events experienced by participant - experimental arm only

  From start of chemoradiation treatment through 90 days

• Late toxicity as measured by number of late adverse events experienced by participant - experimental arm only

  From day 91 through 24 months after completion of chemoradiation

• Overall survival (OS)

  Through completion of follow-up (estimated to be 24 months and 9 weeks)

Study Arms (2)

Control Arm: Standard of Care Chemoradiation

ACTIVE COMPARATOR

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

Radiation: Radiation treatment; Drug: Cisplatin

Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation

EXPERIMENTAL

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

Drug: Telaglenastat; Radiation: Radiation treatment; Drug: Cisplatin

Interventions

Telaglenastat DRUG

-800 mg twice per day by mouth

Also known as: CB-893

Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation

Radiation treatment RADIATION

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

Control Arm: Standard of Care Chemoradiation; Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation

Cisplatin DRUG

* Standard of care * Weekly administration of cisplain

Control Arm: Standard of Care Chemoradiation; Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator
• Calithera Biosciences, Inc: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

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

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Radiotherapy; Cisplatin

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Officials

• Julie K Schwarz, M.D., Ph.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

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

CONTACT

314-608-6813; jschwarz@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization will occur on a 5:1 basis to experimental arm and control arm. The first 5 participants randomized to the experimental arm will be considered the safety lead-in.

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: August 30, 2022
• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): October 7, 2032
• Study Completion (Estimated): October 7, 2032
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)