Overview

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)