CAPTEM for Glioblastoma

(CAPTEM Trial)

Overseen By John Boockvar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Northwell Health

Must be taking: Temozolomide

Must not be taking: Coumadin, Phenytoin

Disqualifiers: Prior chemotherapy, Severe hypersensitivity, others

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

Compensation: Varies

Number of Visits: Unknown

67 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of administering the medication capecitabine along with temozolomide when you start your monthly regimen of oral temozolomide for the treatment of your newly diagnosed glioblastoma multiforme (GBM). Capecitabine is an oral chemotherapy that is given to patients with other types of cancer. The study will evaluate whether the dosage of 1500 mg/m2 of capecitabine is tolerable after radiation, when taken along with temozolomide. It will also try to determine if the medication capecitabine helps patients respond to treatment for a longer period of time compared to just temozolomide alone, which is the standard of care.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot take certain medications like Coumadin and phenytoin due to interactions with capecitabine. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug CAPTEM for treating glioblastoma?

Research shows that temozolomide, a component of CAPTEM, is effective in treating glioblastoma, especially when used with radiotherapy. Studies have found that it can improve survival rates in patients with newly diagnosed glioblastoma, making it a promising option for this condition. ^{1 2 3 4 5}

Is the CAPTEM treatment generally safe for humans?

Temozolomide, a part of the CAPTEM treatment, is generally considered safe but can cause side effects like fatigue, nausea, and blood-related issues such as low platelet and white blood cell counts. Rarely, it can lead to severe blood disorders like aplastic anemia. Capecitabine, the other component, has been studied in combination with temozolomide, and the safety profile is being evaluated to determine the maximum safe dose. ^{1 6 7 8 9}

What makes the CAPTEM drug unique for treating glioblastoma?

CAPTEM combines capecitabine and temozolomide, which may offer a novel approach by using two drugs that work differently: capecitabine is a chemotherapy drug that interferes with DNA production, while temozolomide is an alkylating agent that damages the DNA of cancer cells. This combination could potentially overcome resistance seen in glioblastoma treatments that use temozolomide alone. ^{6 10 11 12 13}

Research Team

John Boockvar, MD

Principal Investigator

Lenox Hill Hospital-Northwell Health

Eligibility Criteria

This trial is for adults aged 18-74 with newly diagnosed Glioblastoma Multiforme who've finished initial chemo-radiation but not started maintenance temozolomide. Participants must be able to take oral medication, have a life expectancy over 3 months, use effective contraception if applicable, and have good organ function. Exclusions include prior treatment with similar drugs, serious illnesses or conditions that interfere with consent or treatment, recent other cancers (except certain treated cases), pregnancy/lactation, and severe drug allergies.

Inclusion Criteria

Agree to use effective barrier contraception while on treatment and for 2 months thereafter if of childbearing potential

I understand the study and can agree to participate.

I have been diagnosed with a type of brain tumor called Glioblastoma.

Exclusion Criteria

I need assistance with my daily activities.

I have heart disease and need a heart doctor's approval before starting capecitabine.

I have had chemotherapy with capecitabine or temozolomide for another cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation and Concurrent Temozolomide

Participants undergo 6 weeks of radiation therapy with a concurrent daily dose of temozolomide

6 weeks

Rest Period

Participants have a one-month rest period with no treatment

4 weeks

Maintenance Treatment

Participants receive maintenance temozolomide and capecitabine, with temozolomide given five days out of every 28 days, for a minimum of six months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Capecitabine
• Temozolomide

Trial Overview The study tests the safety and effectiveness of capecitabine combined with temozolomide in treating new glioblastoma multiforme after radiation therapy. It aims to see if adding capecitabine improves patient response compared to standard care which is just temozolomide alone.

Participant Groups

Group I: Capecitabine amd Temozolomide Experimental Treatment 2 Interventions

Oral Capecitabine at 1500 mg/m2 divided into twice daily dosing, taken on days 1-14, and Temozolomide at 150 mg/m2 - 200 mg/m2 divided into twice daily dosing, taken on days 10-14; days 15-28 off.

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

Approved in European Union as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in United States as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Canada as Xeloda for:

• Colorectal cancer
• Breast cancer

Approved in Japan as Xeloda for:

• Colorectal cancer
• Breast cancer

Who Is Running the Clinical Trial?

Northwell Health

Lead Sponsor

Trials

481

Recruited

470,000+

Findings from Research

Temozolomide is primarily used for treating refractory central nervous system cancers like anaplastic astrocytoma and glioblastoma, but ongoing clinical trials are exploring its efficacy and safety in newly diagnosed gliomas and other types of tumors.

Research is also investigating different dosing schedules and combinations with other treatments, suggesting that temozolomide could be a versatile option in cancer therapy beyond its current approved uses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future directions for temozolomide therapy. Yung, WK.[2019]

In a study of 30 patients with recurrent glioblastoma treated with a 5-day regimen of temozolomide (TMZ), the overall response rate was 23.5%, with a median overall survival of 9.9 months, indicating moderate efficacy in this patient population.

Low expression of the MGMT protein was associated with significantly better progression-free survival and overall survival, highlighting its role as an important prognostic factor for patients receiving TMZ after nitrosourea-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide. Nagane, M., Kobayashi, K., Ohnishi, A., et al.[2018]

Temozolomide has been established as an effective treatment for newly diagnosed glioblastoma, marking a significant advancement in the standard of care for this aggressive brain tumor.

The presence of epigenetic silencing of the MGMT gene in tumor specimens is a strong prognostic factor for survival and indicates which patients are likely to benefit from treatment with temozolomide, highlighting the importance of personalized medicine in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Insight: temozolomide as a treatment for malignant glioma--impact of a recent trial. Mason, WP., Cairncross, JG.[2018]

In a phase II clinical trial involving 21 patients with newly diagnosed glioblastoma multiforme (GBM), the combination of temozolomide (TMZ) with radiotherapy resulted in a one-year survival rate of 58% and a median survival time of 15.7 months, indicating its efficacy in extending survival.

The treatment regimen was well-tolerated, with only mild to moderate non-hematological side effects and minimal severe hematological toxicity, suggesting that TMZ has a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. Lanzetta, G., Campanella, C., Rozzi, A., et al.[2018]

Temozolomide, a new chemotherapy drug, was tested on 16 patients with recurrent glioblastoma multiforme, showing a median overall survival of 6.5 months and a 1-year survival rate of 16%.

The survival outcomes with temozolomide were comparable to other studies, indicating its potential effectiveness, and suggesting the need for further randomized trials to explore its use in initial treatment and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution. Teixeira, MM., Garcia, I., Portela, I., et al.[2018]

The study confirmed that the generic temozolomide capsules (TOZ039) are bioequivalent to the brand Temodal® capsules, with pharmacokinetic parameters falling within the acceptable range for both 20-mg and 100-mg doses in 29 patients with brain tumors.

The treatment was found to be safe, with no treatment-related severe adverse events or mortality reported, although 82.8% of patients experienced some adverse effects, highlighting the importance of monitoring patient responses during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. Hu, C., Lin, Q., Liu, C., et al.[2021]

In a study of 87 newly diagnosed glioblastoma patients, only 5% experienced severe myelotoxicity during treatment with temozolomide (TMZ) and radiation therapy, indicating that while the risk exists, it is relatively low.

Factors such as female sex, low pretreatment platelet counts, and specific genetic markers were identified as potential predictors of severe myelotoxicity, suggesting that personalized treatment approaches could help mitigate risks in vulnerable patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. Lombardi, G., Rumiato, E., Bertorelle, R., et al.[2018]

In a Phase I clinical trial involving 24 patients with brain metastases from breast cancer, the combination of temozolomide and capecitabine demonstrated significant antitumor activity, achieving an 18% objective response rate with 1 complete and 3 partial responses.

The treatment was well-tolerated, with fatigue and nausea being the most common side effects, and it showed potential for maintaining or improving neurocognitive function in patients with stable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. Rivera, E., Meyers, C., Groves, M., et al.[2018]

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]

In a study of 44 patients with glioblastoma multiforme (GBM), the combination of thalidomide and temozolomide significantly improved median survival (103 weeks) and time to tumor progression (36 weeks) compared to thalidomide alone (63 weeks and 17 weeks, respectively).

The combination treatment was found to be safe and well tolerated, with mild to moderate side effects, suggesting that this approach could be a promising strategy for enhancing treatment efficacy in GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined thalidomide and temozolomide treatment in patients with glioblastoma multiforme. Baumann, F., Bjeljac, M., Kollias, SS., et al.[2019]

In a phase II trial involving 88 patients with recurrent malignant gliomas, the combination of temozolomide (TMZ) and 13-cis-retinoic acid (cRA) demonstrated a progression-free survival (PFS) rate of 43% at 6 months, indicating significant efficacy in this difficult-to-treat population.

The treatment was generally well-tolerated, with low rates of severe side effects, such as granulocytopenia (1.8%) and thrombocytopenia (1.4%), suggesting that the combination therapy is a viable option for patients with recurrent malignant gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. Jaeckle, KA., Hess, KR., Yung, WK., et al.[2022]

Temozolomide (TMZ) is an effective chemotherapy for glioblastoma, but many glioma cells develop resistance to it, often linked to increased levels of the enzyme MGMT.

In a study comparing drug-resistant U251 glioma cells to their parental counterparts, the resistant cells showed increased connexin 43 expression and reduced migratory activity, indicating distinct biological changes associated with drug resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Characterization of Temozolomide-Resistant Human Glioma Cells. Lai, SW., Huang, BR., Liu, YS., et al.[2018]

In a study of 46 patients with newly diagnosed glioblastoma multiforme, the combination of temozolomide and thalidomide resulted in a median survival time of 13 months, which is only slightly better than the 12 months achieved with temozolomide alone.

While both treatment regimens produced similar survival outcomes, the combination therapy with thalidomide was associated with a moderate increase in toxicity, indicating no significant advantage in efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Temozolomide and thalidomide in the treatment of glioblastoma multiforme. Riva, M., Imbesi, F., Beghi, E., et al.[2018]

References

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

Future directions for temozolomide therapy. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Prognostic significance of O6-methylguanine-DNA methyltransferase protein expression in patients with recurrent glioblastoma treated with temozolomide. [2018]

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

Drug Insight: temozolomide as a treatment for malignant glioma--impact of a recent trial. [2018]

4. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide in radio-chemotherapy combined treatment for newly-diagnosed glioblastoma multiforme: phase II clinical trial. [2018]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Temozolomide in second-line treatment after prior nitrosurea-based chemotherapy in glioblastoma multiforme: experience from a Portuguese institution. [2018]

6. Germany pubmed.ncbi.nlm.nih.gov

Bioequivalence study of 20-mg and 100-mg temozolomide capsules (TOZ309 and Temodal®) in glioma patients in China. [2021]

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

Clinical and Genetic Factors Associated With Severe Hematological Toxicity in Glioblastoma Patients During Radiation Plus Temozolomide Treatment: A Prospective Study. [2018]

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

Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Temozolomide-induced aplastic anaemia: Case report and review of the literature. [2022]

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

Combined thalidomide and temozolomide treatment in patients with glioblastoma multiforme. [2019]

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

Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Differential Characterization of Temozolomide-Resistant Human Glioma Cells. [2018]

13. Greece pubmed.ncbi.nlm.nih.gov

Temozolomide and thalidomide in the treatment of glioblastoma multiforme. [2018]