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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with newly diagnosed glioblastoma, an aggressive brain cancer. Researchers aim to determine if adding capecitabine, a chemotherapy drug, to the standard treatment of temozolomide enhances patient outcomes. The goal is to assess whether this combination is both safe and more effective in delaying cancer growth compared to temozolomide alone. Suitable candidates have completed initial chemo-radiation and have not yet started maintenance treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new combination therapy.

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.

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

Research shows that patients generally tolerate the combination of capecitabine and temozolomide well. In past studies, no severe side effects, such as those classified as grade 4 or 5, were reported. The most common side effect was nausea, affecting about 42% of patients.

Capecitabine is already used safely for other types of cancer, indicating it is well-tolerated. When combined with temozolomide, it has shown promising results in controlling cancer for longer periods without worsening. This suggests the combination might offer benefits without introducing many new risks.

Participants should discuss any concerns with the study team and their doctor to understand what these findings mean personally. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for glioblastoma?

Unlike the standard treatments for glioblastoma, which typically involve surgery, radiation, and chemotherapy with drugs like temozolomide alone, the combination of Capecitabine and Temozolomide is unique because it targets the cancer cells at different stages of their life cycle. Capecitabine is converted into 5-fluorouracil (5-FU) within the tumor, disrupting its DNA synthesis, while Temozolomide adds an extra punch by further damaging the DNA of rapidly dividing cancer cells. Researchers are excited about this combo because it might enhance the effectiveness of treatment by attacking the tumor cells more comprehensively, potentially improving outcomes for patients with this aggressive brain cancer.

What evidence suggests that this treatment might be an effective treatment for glioblastoma?

This trial will evaluate the combination of capecitabine and temozolomide for treating glioblastoma. Research has shown that using these drugs together yields promising results for certain cancers. Studies have found that this combination can help patients live longer without their cancer worsening, compared to using temozolomide alone. For glioblastoma patients, evidence indicates that this combination makes cancer cells more responsive to treatment. Specifically, research has noted that patients on this treatment plan have a median time of about 10.6 months before the cancer progresses. While these findings are encouraging, they are part of ongoing research to find the best treatment for glioblastoma. ^{1 2 3 4 6}

Who Is on the Research Team?

John Boockvar, MD

Principal Investigator

Lenox Hill Hospital-Northwell Health

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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 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]

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 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]

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]

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, 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10546829/

Efficacy of Capecitabine and Temozolomide Regimen in ... Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.01013

Randomized Study of Temozolomide or ... The combination of capecitabine/temozolomide was associated with a significant improvement in PFS compared with temozolomide alone in patients with advanced ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5557017/

Combination of 6-thioguanine, capecitabine, and celecoxib ... A recent long-term follow-up of these patients showed a 5-year survival rate of 10% for glioma patients receiving radiotherapy with concomitant and adjuvant ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03213002

Study Details | NCT03213002 | Oral Capecitabine and ... This trial proposes to improve the current standard of care by enhancing the efficacy of an active drug temozolomide, currently used for treatment of GBM.

5. nature.com nature.com/articles/s41420-025-02664-w

GLUT3 enhances chemosensitivity in glioblastoma by ... This study demonstrates that GLUT3 upregulation in GBM cells enhances sensitivity to both TMZ and capecitabine (CAPE). Uptake assays revealed ...

6. clinicaloncologyonline.net clinicaloncologyonline.net/article/S0936-6555(22)00503-9/fulltext

Preoperative Chemoradiotherapy With Capecitabine With ... There were no treatment-related NCI-CTCAE grade 4 or 5 adverse events. Nausea was the most common adverse event, occurring in 25 cases (41.7%).