Glutaminase Inhibitor + Chemoradiation for Cervical Cancer

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

42 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment Glutaminase Inhibitor + Chemoradiation for Cervical Cancer?

Research shows that using cisplatin with radiation therapy significantly improves survival rates in cervical cancer patients compared to radiation alone. Cisplatin acts as a potent sensitizer, enhancing the effects of radiation, and has been a standard treatment for over two decades. ^{1 2 3 4 5}

What safety data exists for the combination of glutaminase inhibitor, cisplatin, and radiation therapy in cervical cancer treatment?

Studies show that combining cisplatin with radiation therapy for cervical cancer is generally safe, with common side effects including nausea, vomiting, and anemia. Long-term effects can include gastrointestinal and urological issues, but adding cisplatin does not seem to increase these late toxicities. ^{1 2 6 7 8}

What makes the Glutaminase Inhibitor + Chemoradiation treatment for cervical cancer unique?

This treatment is unique because it combines a glutaminase inhibitor with chemoradiation, potentially enhancing the effectiveness of traditional chemotherapy and radiation by targeting cancer cell metabolism, which is different from standard treatments that typically use cisplatin alone or with other drugs like paclitaxel. ^{1 2 9 10 11}

What is the purpose of this trial?

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.

Research Team

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

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I study with weekly cisplatin-paclitaxel and concurrent radiotherapy in patients with carcinoma of the cervix uteri. [2020]

2. Singapore pubmed.ncbi.nlm.nih.gov

Radiation therapy with concomitant and adjuvant cisplatin and paclitaxel in high-risk cervical cancer: long-term follow-up. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Chemoradiotherapy for cervical cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Propensity score matching analysis to comparing cisplatin versus nedaplatin based doublet agent concurrent chemoradiotherapy for locally advanced cervical cancer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Novel approaches for concurrent irradiation in locally advanced cervical cancer: platinum combinations, non-platinum-containing regimens, and molecular targeted agents. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Advanced cervical cancer therapy: concurrent radiation therapy and cisplatin chemotherapy for advanced cervical cancer--a toxicity report. [2013]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Acute and long-term toxicity following radiotherapy alone or in combination with chemotherapy for locally advanced cervical cancer. [2019]

8. England 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. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Phase I/II study of intravenous nedaplatin and intraarterial cisplatin with transcatheter arterial embolization for patients with locally advanced uterine cervical carcinoma. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

[Concurrent chemoradiotherapy for advanced cervical cancer--a pilot study]. [2013]

11. Singapore pubmed.ncbi.nlm.nih.gov

Concurrent chemoradiation with carboplatin for elderly, diabetic and hypertensive patients with locally advanced cervical cancer. [2020]