Vorinostat + Temozolomide for Brain Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores the combination of two chemotherapy drugs, vorinostat and temozolomide, to determine the optimal dose and understand their side effects in treating brain cancers like glioblastoma. These drugs aim to stop tumor growth by killing cancer cells or preventing them from dividing. The trial targets individuals with specific malignant brain tumors, such as glioblastoma, who have already received treatments like radiation. Participants should generally be in stable condition after previous treatments and should not have progressed on temozolomide. 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 have to stop taking my current medications for the trial?
The trial does not specify if you need to stop taking your current medications, but you should not be on any investigational agents or valproic acid for at least 2 weeks before enrolling. It's best to discuss your current medications with the study team to ensure they don't interfere with the trial.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that the combination of vorinostat and temozolomide is generally well-tolerated by patients with high-grade gliomas, a type of brain cancer. Many patients do not experience severe side effects from this treatment, though some may have manageable side effects with proper care.
The FDA has already approved vorinostat for another condition, indicating its safety for human use in other situations. Temozolomide is commonly used in brain cancer treatments and is also considered safe. In a clinical trial for these treatments, doctors closely monitor any side effects, ensuring patient safety remains a top priority.12345Why are researchers excited about this trial's treatments?
Researchers are excited about combining vorinostat with temozolomide for brain cancer treatment because this combo targets cancer cells differently than traditional therapies. Most standard treatments, like radiation and chemotherapy, attack rapidly dividing cells, but vorinostat works by altering gene expression, making cancer cells more susceptible to temozolomide. This dual approach may enhance the effectiveness of treatment, potentially leading to better outcomes for patients with brain cancer. Additionally, vorinostat’s ability to modulate gene expression offers a novel mechanism that could overcome resistance seen with existing therapies.
What evidence suggests that vorinostat and temozolomide might be effective for brain cancer?
Research has shown that using vorinostat with temozolomide, the combination under study in this trial, may effectively treat aggressive brain tumors. Vorinostat increases tumor cell sensitivity to treatment by blocking enzymes necessary for their growth, enhancing the effectiveness of temozolomide, a chemotherapy drug. Studies have found that patients generally tolerate this combination well. Vorinostat may also boost the effects of radiation therapy by disrupting the tumor cells' DNA repair mechanisms. While more research is needed, early results suggest this combination could effectively target brain cancer cells.12456
Who Is on the Research Team?
Patrick Y Wen
Principal Investigator
National Cancer Institute (NCI)
Are You a Good Fit for This Trial?
This trial is for patients with certain types of brain tumors, including glioblastoma and anaplastic astrocytoma. Participants must have a life expectancy over 8 weeks, be able to perform daily activities at least partially independently (Karnofsky score >=60), and have adequate blood cell counts and organ function. Pregnant or breastfeeding women, HIV-positive patients on antiretrovirals, those with recent other cancers or serious illnesses affecting the study's safety are excluded.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Patients receive vorinostat and temozolomide in a dose-escalation study, with treatment repeating every 28 days for up to 13 courses
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Temozolomide
- Vorinostat
Trial Overview
The trial is testing the combination of two chemotherapy drugs: Vorinostat and Temozolomide. It aims to find the safest dose that can effectively treat malignant gliomas by killing tumor cells or stopping their growth. The study will also look into how these drugs affect enzymes related to cell growth.
How Is the Trial Designed?
1
Treatment groups
Experimental Treatment
PART I: Patients receive vorinostat PO QD or BID on days 1-7 and 15-21 OR QD or BID on days 1-7. Patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Treatment may continue beyond 13 courses at the discretion of the investigator. PART II: Patients receive vorinostat and temozolomide as in part I\*. \[Note: Beginning in course 2, some patients may receive a higher dose of temozolomide.\]
Temozolomide is already approved in European Union, United States for the following indications:
- Newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and subsequently as monotherapy treatment
- Children from the age of three years, adolescents and adults with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy
- Newly diagnosed glioblastoma concomitantly with radiotherapy and subsequently as monotherapy treatment
- Newly diagnosed or refractory anaplastic astrocytoma
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor
Citations
North American Brain Tumor Consortium Study 04-03 - PMC
Vorinostat in combination with temozolomide is well-tolerated in patients with HGG. A phase I/II trial of vorinostat with radiotherapy and concomitant TMZ in ...
Vorinostat and Temozolomide in Treating Patients With ...
This phase I trial is studying the side effects and best dose of vorinostat when given together with temozolomide in treating patients with malignant ...
Phase I/II trial of vorinostat combined with temozolomide and ...
This trial evaluated the MTD and efficacy of vorinostat, an HDAC inhibitor with radiosensitizing properties, combined with standard chemoradiation, in patients ...
Vorinostat as a radiosensitizer for CNS malignancies
Conclusions: Preclinical studies demonostrated that vorinostat profoundly decrease expression of key genes involved in DNA repair, inhibiting the repair of DNA ...
Inhibition of glioblastoma cell proliferation, invasion, and ...
... brain tumors and current therapies with temozolomide or suberoylanilide hydroxamic acid (SAHA, vorinostat) show considerable limitations
Vorinostat, Temozolomide, and Radiation Therapy in ...
This phase I/II trial studies the side effects and best dose of vorinostat when given together with temozolomide and radiation therapy and to see how well ...
Unbiased Results
We believe in providing patients with all the options.
Your Data Stays Your Data
We only share your information with the clinical trials you're trying to access.
Verified Trials Only
All of our trials are run by licensed doctors, researchers, and healthcare companies.