Telaglenastat + Radiation Therapy + Temozolomide for Astrocytoma

Not currently recruiting at 29 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Investigational agents

Disqualifiers: Prior chemotherapy, Prior brain radiation, Uncontrolled illness, Active malignancy, others

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

Compensation: Varies

Number of Visits: 3

Duration: 5.5-6.5 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for certain brain tumors called IDH-mutated astrocytomas. It combines telaglenastat, an experimental drug, with radiation therapy and the common chemotherapy drug temozolomide to determine if this combination outperforms current treatments. Telaglenastat may inhibit tumor growth by blocking specific enzymes essential for cancer cell growth. The trial seeks participants with confirmed IDH-mutated diffuse or anaplastic astrocytoma who have not undergone previous chemotherapy or radiation for their glioma and can swallow pills without difficulty. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must be on a stable or decreasing dose of corticosteroids and antiepileptic therapy before joining the trial.

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

Research has shown that telaglenastat, when combined with radiation therapy, appears safe. In a previous study, patients tolerated telaglenastat well with standard radiation doses.

Temozolomide, the chemotherapy drug in this trial, is well-known for treating brain cancers. It has proven effective and generally safe for patients with these conditions. While side effects like nausea or tiredness can occur, they are usually manageable.

These findings suggest that the combination treatment in this trial could be safe for participants. However, as this is an early-phase trial, monitoring for any new or unexpected side effects is crucial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about telaglenastat combined with radiation therapy and temozolomide for astrocytoma because it targets cancer cells in a new way. Unlike traditional treatments, which often focus solely on killing rapidly dividing cells, telaglenastat inhibits a specific enzyme that cancer cells need to thrive. This approach could make the cancer cells more vulnerable to radiation and chemotherapy. By blocking this enzyme, telaglenastat may enhance the effectiveness of existing treatments, potentially leading to better outcomes for patients with astrocytoma.

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

Studies have shown that combining temozolomide with radiation extends the lives of patients with certain brain tumors. Specifically, for patients with a particular type of astrocytoma, this combination improved survival times compared to temozolomide alone. In this trial, participants will receive a combination of telaglenastat, temozolomide, and radiation therapy. Telaglenastat blocks enzymes that tumor cells need for growth. Early research suggests that adding telaglenastat to radiation and temozolomide may be more effective than using radiation and temozolomide alone. This combination is under study because it attacks tumor cells in different ways, potentially halting their growth more effectively. ^{1 2 3 4 6}

Who Is on the Research Team?

Sani Kizilbash, MD, MPH

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for patients with IDH-mutated diffuse or anaplastic astrocytoma. They must have certain blood levels, organ function, and no evidence of tumor in the lower brain or spine. Participants need to be over 16 years old, not pregnant, willing to use contraception, and able to give consent. Those with severe illnesses or a second active cancer are excluded.

Inclusion Criteria

My cancer has a specific IDH mutation.

I am on a stable blood thinner dose without bleeding or clotting issues.

Hemoglobin > 9.0 g/dL (within 14 days prior to registration)

Exclusion Criteria

I have never used Gliadel wafers.

I am not pregnant or breastfeeding.

I have not had radiation therapy to my brain or overlapping areas of my head and neck.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive telaglenastat orally twice daily, temozolomide once daily, and undergo radiation therapy 5 days a week for up to 5.5 weeks (diffuse astrocytoma) or 6.5 weeks (anaplastic astrocytoma)

5.5-6.5 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Radiation Therapy
• Telaglenastat Hydrochloride
• Temozolomide

Trial Overview The trial tests telaglenastat combined with radiation therapy and temozolomide chemotherapy on patients with specific types of brain tumors (astrocytomas). It aims to find the best dose of telaglenastat that's effective when used alongside standard treatments like surgery and radiation.

How Is the Trial Designed?

Group I: Treatment (telaglenastat, temozolomide, RT) Experimental Treatment 4 Interventions

Patients receive telaglenastat PO BID 7 days a week, temozolomide PO QD 7 days a week, and undergo RT 5 days a week for up to 5.5 weeks (diffuse astrocytoma) or 6.5 weeks (anaplastic astrocytoma) in the absence of disease progression or unacceptable toxicity.

Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in United States as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Canada as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Japan as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in China as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Approved in Switzerland as Radiation Therapy for:

• Cancer treatment
• Palliative care
• Oropharyngeal cancer
• Breast cancer
• Prostate cancer
• Lung cancer
• Brain tumors

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a randomized trial involving 144 patients with anaplastic astrocytoma (AA) and glioblastoma (GBM), neoadjuvant temozolomide (NeoTMZ) did not show a survival advantage for the overall population or for GBM patients compared to radiotherapy alone.

However, patients with AA who received NeoTMZ had a significantly longer median survival of 95.1 months compared to 35.2 months for those receiving only radiotherapy, indicating a potential benefit of NeoTMZ specifically for AA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial. Malmström, A., Poulsen, HS., Grønberg, BH., et al.[2018]

The combination of temozolomide and radiation therapy is safe and well tolerated in patients with newly diagnosed glioblastoma, with only mild to moderate nonhematologic toxicities observed during treatment.

Patients treated with this regimen had a median survival of 16 months, with 58% surviving at one year and 31% at two years, indicating that this treatment may effectively prolong survival, especially in younger patients and those who had surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide. Stupp, R., Dietrich, PY., Ostermann Kraljevic, S., et al.[2022]

In a study of 9 patients with brain metastases from lung adenocarcinoma, the combination of intensity-modulated radiation therapy (IMRT) and temozolomide (TMZ) resulted in a high objective response rate of 77.8%, with one complete response and six partial responses, confirming the efficacy of this treatment approach.

Patients receiving the combination treatment experienced fewer severe adverse effects compared to those who only received IMRT, with no grade ≥3 hematologic toxicities reported, and an improvement in quality of life was noted, indicating that the addition of TMZ is both effective and relatively safe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated radiation therapy combined with concomitant temozolomide for brain metastases from lung adenocarcinoma. Li, J., Chai, X., Cao, Y., et al.[2020]

Temozolomide (TMZ) is generally safe with mild to moderate side effects, but this case report highlights a rare instance of severe aplastic anemia (AA) in a 68-year-old female patient following treatment for glioblastoma, indicating a potential serious risk associated with the drug.

The patient's AA was managed successfully with supportive care, including platelet transfusions and growth factor treatment, and her blood counts returned to normal within 38 days, emphasizing the importance of monitoring blood parameters during and after TMZ treatment to detect such rare toxicities early.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. Gilbar, PJ., Pokharel, K., Mangos, HM.[2022]

Temozolomide (TMZ) enhances the effectiveness of radiation therapy in treating glioblastoma cells, leading to a significant reduction in colony formation when combined with irradiation, compared to either treatment alone.

While irradiation was more toxic to glioma cells than TMZ, the combination of both treatments increased the sensitivity of glioma cells to radiation, suggesting a potential strategy for improving glioblastoma treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay. Babaloui, S., Najafi, M., Mozdarani, H., et al.[2022]

Temozolomide (TMZ) is an effective oral treatment for malignant gliomas, providing significant survival benefits while being generally well tolerated by patients.

While most side effects of TMZ are mild to moderate, there is a risk of severe hematologic adverse events, such as myelodysplastic syndrome and aplastic anemia, which have been documented in the literature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-related hematologic toxicity. Scaringi, C., De Sanctis, V., Minniti, G., et al.[2018]

In a retrospective study of 62 patients with anaplastic glioma, the combination of temozolomide (TMZ) and radiation therapy (RT) did not show a significant improvement in progression-free survival compared to RT alone, with median times of 14.8 months for TMZ-RT and 16.7 months for RT alone.

However, patients receiving TMZ-RT had a longer median overall survival of 34.1 months compared to 27.4 months for those treated with RT alone, suggesting a potential benefit of the combination therapy that warrants further investigation through prospective randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined temozolomide and radiation as an initial treatment for anaplastic glioma. Tham, CK., See, SJ., Tan, SH., et al.[2018]

In a study of 165 glioblastoma patients, the extent of tumor resection was the only factor associated with longer survival, indicating that surgical removal of the tumor is crucial for improving outcomes.

The use of Gliadel wafers significantly increased the risk of adverse events, especially in patients with recurrent tumors, with those receiving eight wafers facing a 3-fold higher risk of adverse events and a 5.6-fold higher risk of site-related complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of Gliadel wafers for newly diagnosed and recurrent glioblastoma. De Bonis, P., Anile, C., Pompucci, A., et al.[2018]

The combination of Gliadel wafers with concurrent radio-chemotherapy using temozolomide (TMZ) in 24 patients with glioblastoma multiforme resulted in a median overall survival of 19.2 months and a median progression-free survival of 12.3 months, indicating a potential benefit of this treatment approach.

While the treatment was generally well tolerated, 10 patients experienced significant toxicity leading to premature discontinuation of TMZ, highlighting the need for careful monitoring of hematological and digestive side effects during this multimodal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the per-operatory application of GLIADEL wafers (BCNU, carmustine) in combination with temozolomide and radiotherapy in patients with glioblastoma multiforme: efficacy and toxicity. Miglierini, P., Bouchekoua, M., Rousseau, B., et al.[2018]

In a study of 67 patients with low-grade pituitary tumors, the combination of temozolomide (TMZ) and radiotherapy showed a significantly higher total effective rate (91.89%) compared to radiotherapy alone (70.00%).

The combined treatment resulted in greater reductions in serum levels of prolactin, insulin-like growth factor-1, and growth hormone, indicating enhanced efficacy in managing hormone levels associated with pituitary tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Trail Investigating Temozolomide Neoadjuvant Chemotherapy Combined with Radiotherapy in Low-Grade Pituitary Tumors. Cui, J., Shen, J., Ru, X., et al.[2022]

Temozolomide (TMZ) can cause severe drug-induced toxic hepatitis, as demonstrated in a case where a patient developed significant liver issues after 5 weeks of treatment for glioblastoma, highlighting the importance of monitoring liver function during therapy.

To prevent serious complications, including potentially life-threatening conditions, it is crucial to monitor liver enzyme levels twice weekly during TMZ treatment and to discontinue the drug immediately if hepatitis is suspected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide-induced liver damage. A case report. Becker, F., Hecht, M., Schmidtner, J., et al.[2021]

In a study of 27 patients with newly diagnosed high-grade gliomas, the combination of temozolomide (TMZ) and radiation therapy (RT) demonstrated promising efficacy, with a median overall survival of 19 months and a one-year survival rate of 81.2%.

The treatment was well tolerated with no drug toxicity-related mortality, indicating a favorable safety profile, especially in patients under 50 years old and those who had debulking surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The outcomes of concomitant radiation plus temozolomide followed by adjuvant temozolomide for newly diagnosed high grade gliomas: the preliminary results of single center prospective study. Shawky, H., Abo Hamar, AH., Galal, S., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03528642

Telaglenastat With Radiation Therapy and Temozolomide ... Giving telaglenastat with radiation therapy and temozolomide may work better than surgery, radiation therapy, and temozolomide in treating patients with IDH- ...

2. clinicaltrials.ucsd.edu clinicaltrials.ucsd.edu/trial/NCT03528642

Telaglenastat With Radiation Therapy and Temozolomide ... This phase 1b trial studies the side effects and best dose of telaglenastat in combination with radiation therapy and temozolomide in treating patients with ...

3. dana-farber.org dana-farber.org/clinical-trials/19-666

A Phase 1b Trial of CB-839 in Combination with Radiation ... This phase 1b trial studies the side effects and best dose of telaglenastat in combination with radiation therapy and temozolomide in treating patients with ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03528642?tab=history&a=98

Record History | ver. 98: 2023-09-12 | NCT03528642 Patients receive telaglenastat PO BID 7 days a week, temozolomide PO QD 7 days a week, and undergo RT 5 days a week for up to 5.5 weeks (diffuse astrocytoma) or ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9661046/

CTNI-23. PRELIMINARY SAFETY AND ... A phase I clinical trial investigating the safety and tolerability of telaglenastat administered orally concurrently with standard doses of radiation.

6. researchgate.net researchgate.net/publication/365386149_CTNI-23_PRELIMINARY_SAFETY_AND_PHARMACOKINETICS_DATA_FOR_A_PHASE_1B_TRIAL_OF_TELAGLENASTAT_IN_COMBINATION_WITH_RADIATION_THERAPY_AND_TEMOZOLOMIDE_IN_PATIENTS_WITH_IDH-MUTANT_GRADE_23_ASTROCYTOMA_NCI-1

CTNI-23. PRELIMINARY SAFETY AND ... Purpose To report the long-term outcomes in adult patients with grade 2 IDH-mutant astrocytoma treated with temozolomide (TMZ)-based ...