Vorinostat + Isotretinoin + Temozolomide for Glioblastoma
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests whether a combination of three drugs—vorinostat (a type of histone deacetylase inhibitor), isotretinoin, and temozolomide—can help control glioblastoma or gliosarcoma, aggressive brain tumors. Researchers are also assessing the safety of this drug combination for patients. Individuals with glioblastoma or gliosarcoma that has recurred or progressed after radiation therapy, and who have already tried other treatments, might be suitable candidates for this trial. 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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop all current medications, but you cannot take valproic acid (an anticonvulsant) unless switched to another drug before starting the trial. Also, if you are on enzyme-inducing anti-epileptic drugs, your doctor might need to monitor your drug levels.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research has shown that the combination of vorinostat, isotretinoin, and temozolomide has been studied for safety in patients with high-grade gliomas. Vorinostat, tested in several studies, is generally considered safe but can cause side effects like tiredness and nausea. Isotretinoin, often used for other conditions, may lead to side effects such as dry skin or increased sensitivity to sunlight. Temozolomide, approved by the FDA for treating glioblastoma, is usually well-tolerated, though it may cause issues like low blood cell counts.
One study showed that the combination of vorinostat, isotretinoin, and temozolomide reduced tumor cell survival. However, other trials indicate that adding isotretinoin to temozolomide might not always be beneficial and could be harmful in some cases. These findings suggest that while the treatments have potential, risks exist, and side effects vary from person to person.12345Why are researchers excited about this trial's treatments?
Researchers are excited about these treatments because they combine known cancer-fighting drugs in innovative ways to tackle glioblastoma, a particularly aggressive brain cancer. Unlike the standard treatments like radiation and surgery, which can be limited in their effectiveness, these combinations utilize isotretinoin, temozolomide, and vorinostat to potentially enhance anti-tumor activity. Vorinostat, in particular, works by inhibiting enzymes that cancer cells need to grow, offering a novel mechanism of action compared to traditional therapies. By targeting the cancer cells more directly and possibly improving the effectiveness of existing drugs, these combinations could lead to more effective treatment options for patients with glioblastoma.
What evidence suggests that this trial's treatments could be effective for glioblastoma?
Research shows that vorinostat, a type of drug, may help treat glioblastoma by slowing and stopping tumor growth. Studies have found that vorinostat can make glioblastoma cells less likely to survive and can even cause them to die. Temozolomide, a well-known chemotherapy drug, effectively treats glioblastoma by damaging the DNA of cancer cells, preventing their growth. Isotretinoin, commonly used for severe acne, has also shown some potential against glioblastoma when used alone.
In this trial, participants will join different treatment arms to evaluate the effectiveness of these drug combinations. One arm will receive temozolomide plus isotretinoin, another will receive vorinostat plus isotretinoin, and a third will receive vorinostat plus isotretinoin plus temozolomide. Combining these treatments might provide a stronger approach by attacking cancer cells in different ways. Early findings suggest that using these treatments together could better control glioblastoma growth.12678Who Is on the Research Team?
Marta Penas-Prado, MD
Principal Investigator
M.D. Anderson Cancer Center
Vinay Puduvalli, MD
Principal Investigator
Brain Tumor Trials Collaborative (BTTC), and Ohio State University
Are You a Good Fit for This Trial?
Adults over 18 with recurrent WHO grade IV glioma (glioblastoma or gliosarcoma) who've failed radiation therapy can join. They must be able to sign consent, have a Karnofsky performance status >=60, stable health post-prior treatments, and agree to contraception. Exclusions include other cancers within 3 years (except certain types), prior bevacizumab treatment, valproic acid use without switching drugs first, inability to tolerate study procedures or swallow tablets.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive vorinostat, isotretinoin, and temozolomide in 28-day cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- Isotretinoin
- Temozolomide
- Vorinostat
Find a Clinic Near You
Who Is Running the Clinical Trial?
M.D. Anderson Cancer Center
Lead Sponsor
Merck Sharp & Dohme LLC
Industry Sponsor
Chirfi Guindo
Merck Sharp & Dohme LLC
Chief Marketing Officer since 2022
Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business
Robert M. Davis
Merck Sharp & Dohme LLC
Chief Executive Officer since 2021
JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University