Glutaminase Inhibitor + Chemoradiation for Cervical Cancer

Not yet recruiting at 1 trial location

Overseen By Julie Schwarz, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must be taking: Chemoradiation

Must not be taking: Investigational agents

Disqualifiers: Active malignancy, Prior pelvic radiation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 9 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding a new drug, telaglenastat (a glutaminase inhibitor), to standard cervical cancer treatments like chemotherapy and radiation can help patients live longer without their cancer worsening. It focuses on those with advanced cervical cancer that hasn't spread beyond the pelvic area. Participants should have newly diagnosed advanced cervical cancer and be eligible for chemoradiotherapy, including brachytherapy, a type of internal radiation. The study compares the effects of the new treatment combination with usual care alone. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on therapeutic anticoagulation, you should be on a stable dose. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that telaglenastat, a drug that blocks a specific enzyme, has been tested in other cancer studies and is generally well-tolerated by patients. In earlier research, patients experienced few serious side effects, indicating it is manageable for most people. Some studies even combined telaglenastat with other treatments, and it still appeared safe.

This trial also includes standard treatment with cisplatin, a common cancer drug that can cause side effects like nausea and tiredness. Researchers are adding telaglenastat to see if it can improve results without adding too much risk. For those considering participation, evidence so far suggests that while telaglenastat can have side effects, they are usually not severe, especially with careful monitoring. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about telaglenastat because it targets cancer cells in a novel way. Unlike traditional treatments for cervical cancer, which typically focus on destroying cancer cells with chemotherapy and radiation, telaglenastat works by inhibiting glutaminase. This enzyme is crucial for cancer cells to produce energy and grow, so blocking it can potentially weaken the cancer cells and make them more susceptible to standard treatments. This new mechanism offers a promising strategy to enhance the effectiveness of existing chemoradiation therapies.

What evidence suggests that this trial's treatments could be effective for cervical cancer?

Research shows that adding telaglenastat, a drug that blocks a nutrient cancer cells need, to standard chemoradiation may help treat advanced cervical cancer. In this trial, participants in the experimental arm will receive telaglenastat with standard chemoradiation. A study with 18 patients showed a high success rate of 92.3% for this combination treatment, with many patients experiencing complete or partial tumor shrinkage. Telaglenastat targets cancer cells that depend on a nutrient called glutamine. This approach aims to make cancer cells more sensitive to radiation and chemotherapy, potentially leading to better results for patients. These early findings are promising for those with cervical cancer resistant to radiation. ^{1 6 7 8 9}

Who Is on the Research Team?

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

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed advanced cervical cancer (stages III-IVA). They must have a certain level of blood cells, liver and kidney function, not be breastfeeding, and able to consent. Excluded are those with severe illnesses, prior treatments for this cancer or pelvic radiation, uncontrolled diabetes or HIV, pregnancy/breastfeeding women, and known allergies to the drugs used.

Inclusion Criteria

Alkaline phosphatase ≤ 2.5 x ULN

Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransfersase (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x ULN

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patient is receiving another investigational agent for the treatment of cancer

Mean resting QTc > 470 msec obtained by electrocardiogram (ECG)

My diabetes is not well-managed, making me unable to undergo a PET scan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 weeks of telaglenastat followed by 7 weeks of standard of care chemoradiation plus telaglenastat

9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months and 9 weeks

Late Toxicity Monitoring

Monitoring for late toxicities related to treatment

24 months after completion of treatment

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Radiation treatment
• Telaglenastat

Trial Overview The study tests if adding telaglenastat (a glutaminase inhibitor) to standard chemoradiation therapy improves progression-free survival in advanced cervical cancer patients compared to historical data of chemoradiation alone. Participants will receive cisplatin chemotherapy alongside radiation treatment.

How Is the Trial Designed?

Group I: Experimental Arm #1: Telaglenastat + Standard of Care Chemoradiation Experimental Treatment 3 Interventions

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

Group II: Control Arm: Standard of Care Chemoradiation Active Control 2 Interventions

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

Cisplatin is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Calithera Biosciences, Inc

Industry Sponsor

Trials

34

Recruited

2,000+

Published Research Related to This Trial

In a pilot study of 24 patients with locally advanced cervical cancer, the combination of Carboplatin or Nedaplatin with conventional radiotherapy resulted in a high response rate, with 9 out of 13 evaluable patients achieving complete responses.

The treatment was found to be safe and well-tolerated, with no significant renal damage or severe hematological toxicity, suggesting that these platinum-based drugs could effectively enhance the efficacy of radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Concurrent chemoradiotherapy for advanced cervical cancer--a pilot study]. Kodama, J., Hashimoto, I., Seki, N., et al.[2013]

The combination of weekly paclitaxel and cisplatin during radiation therapy shows promising efficacy in 'high-risk' cervical cancer patients, with an overall survival rate of 68% at a median follow-up of 58 months.

While hematologic toxicity was common, it was manageable and did not frequently cause treatment delays; however, significant late complications occurred in 52% of patients, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. Argenta, PA., Ghebre, R., Dusenbery, KE., et al.[2020]

A study involving 10 patients with advanced cervical cancer evaluated the safety of combining cisplatin with radiation therapy, finding that most adverse effects were mild (grade 2 or less), with nausea/vomiting being the most common issue.

Despite some cases of anemia being noted as a serious concern, the overall toxicity of the treatment was deemed acceptable, suggesting that larger studies can be conducted to further assess the efficacy of this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. Suggs, CL., Lee, JC., Lewis, GC., et al.[2013]

The maximum-tolerated dose (MTD) of paclitaxel when combined with cisplatin and pelvic radiotherapy for cervical cancer patients was determined to be 50 mg/m2 per week, with diarrhea identified as the main dose-limiting toxicity.

In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating that this regimen could be an effective option for treating locally advanced cervical cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. Pignata, S., Frezza, P., Tramontana, S., et al.[2020]

In a phase I trial involving 21 patients with locally advanced cervical cancer, the maximum tolerated dose (MTD) of weekly paclitaxel in combination with cisplatin was determined to be 40 mg/m², indicating a safe dosage for further studies.

The combination of weekly paclitaxel and cisplatin alongside radiation therapy was feasible and showed an acceptable toxicity profile, with significant side effects like grade 3 proctitis and vaginitis occurring at higher doses of paclitaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maximum tolerated dose and early response - results of a phase I trial of paclitaxel and cisplatin with radiation therapy in carcinoma of the cervix. Prasad, E., Viswanathan, PN., Rangad, VF., et al.[2015]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05521997

Glutaminase Inhibition and Chemoradiation in Advanced ... Study Overview​​ Advanced cervical cancer patients treated with standard of care (SOC) chemoradiation plus glutaminase inhibition with telaglenastat (CB-839) ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8208465/

Glutaminase inhibitors induce thiol-mediated oxidative ... These novel preclinical data support the utility of telaglenastat for glutamine dependent radio-resistant cervical cancers and demonstrate that PI3K pathway ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11926318/

An innovative glutamine metabolism-related gene ... SIRT4 has an anti-cancer role in cervical cancer by inhibiting glutamine metabolism via the MEK/ERK/C-Myc Axis. Anticancer Res. 2024;44(7): ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0014480024000157

Analysis of anti-tumor effect and mechanism of GLS1 ... CB-839 treatment inhibited cancer cell proliferation depending on GLS1 expression in vitro and inhibited tumor growth and metastasis in the CRC mouse model.

5. withpower.com withpower.com/trial/phase-2-cervical-cancers-2023-87875

Glutaminase Inhibitor + Chemoradiation for Cervical Cancer In a study of 18 patients, the combination treatment resulted in a high overall response rate of 92.3%, with 7 complete and 5 partial responses, indicating ...

6. medchemexpress.com medchemexpress.com/CB-839.html?srsltid=AfmBOopMqnnqg_Z6o8GmRzHiZNkwHQhI7igfH5xY8LjAH_tq2fERdGsW

Telaglenastat (CB-839) | GLS1 Inhibitor Advanced Cervical Carcinoma|Cervical Cancer|Cervix Cancer|Cancer of the Cervix ... SAFETY DATA SHEET (SDS). English - EN (393 KB) Français - FR (393 KB) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7897292/

Glutaminase inhibition with telaglenastat (CB-839) ... The glutaminase inhibitor, telaglenastat (CB-839), has been tested in Phase I/II cancer trials and is well tolerated by patients. This study investigated if ...

8. aacrjournals.org aacrjournals.org/cancerres/article/79/4_Supplement/P6-20-07/640138/Abstract-P6-20-07-Efficacy-and-safety-of-CB-839-a

Abstract P6-20-07: Efficacy and safety of CB-839, a small ... In a phase 1 study, the Pac+CB-839 combination was well tolerated and demonstrated clinical activity in a cohort of heavily pretreated pts with ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9437824/

Efficacy and Safety of Telaglenastat Plus Cabozantinib vs ... This randomized clinical trial compares the efficacy and safety of telaglenastat plus cabozantinib vs placebo plus cabozantinib in patients with metastatic ...