Vorinostat Clinical Trials

What Is Vorinostat?

Vorinostat is an FDA-approved medication for cutaneous T-cell lymphoma (CTCL) and mycosis fungoides (MF), which are types of lymphoma affecting the skin. It is a histone deacetylase (HDAC) inhibitor. Vorinostat works by causing chemical changes in proteins attached to DNA, which can alter gene expression. This action is designed to slow the growth of cancer cells or cause them to die by interfering with their multiplication and changing their gene expression profile.

Beyond its approved uses, vorinostat is being investigated in clinical trials for a wide range of other conditions. These include various blood cancers like multiple myeloma and acute myeloid leukemia, solid tumors such as breast cancer, neuroblastoma, prostate cancer, uveal melanoma, and lung cancer, as well as non-cancer conditions like Crohn's disease, ulcerative colitis, Cushing's disease, and schizophrenia.

Uses and Conditions Under Study

Vorinostat has been studied in 272 clinical trials involving 17,692 participants since 2003. These studies explore its potential in numerous conditions, primarily cancers, but also other diseases.

• Blood Cancers: Vorinostat is extensively studied for various blood cancers. It is being investigated for lymphoma in 20 trials, multiple myeloma in 14 trials, and different forms of acute myeloid leukemia (AML) across 42 trials, including recurrent AML and specific genetic subtypes. Researchers believe vorinostat's ability to change the gene expression of leukemia cells may lead to their death, offering a new approach to treatment, particularly in children and young adults with relapsed AML. It is also being studied in acute lymphoblastic leukemia (ALL) in infants.
• Solid Tumors: Vorinostat is under investigation for a variety of solid tumors. This includes 12 trials for unspecified adult solid tumors, 10 trials for breast cancer, and 9 trials for neuroblastoma. Other solid tumors being studied include metastatic castration-resistant prostate cancer, high-risk uveal melanoma, advanced lung cancer, and recurrent ovarian cancer. Vorinostat is thought to help by slowing cancer cell growth, causing cancer cells to die, and potentially making cancer cells more sensitive to radiation therapy.
• Inflammatory Bowel Diseases: Vorinostat is being explored for its potential role in inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. These conditions are characterized by chronic inflammation of the gastrointestinal tract. Studies aim to determine if vorinostat can help control the inflammation and manage symptoms.
• Neurological and Psychiatric Conditions: Clinical trials are also examining vorinostat for non-cancer indications. This includes a pilot study to assess its effectiveness in reducing midnight ACTH levels in patients with Cushing's disease. Additionally, a study is evaluating the safety and tolerability of vorinostat when combined with clozapine treatment in patients with schizophrenia.

Beyond these, vorinostat has been part of safety assessments, such as pharmacokinetic studies in lactating women, to understand how the drug is processed in the body under specific physiological conditions.

Dosing

Vorinostat is available in oral forms, including capsules (marketed as Zolinza Oral Capsules) and oral suspension. The dosage and administration vary significantly depending on the condition being treated and whether it is used alone or in combination with other therapies.

In clinical trials, vorinostat has been studied at various strengths and schedules. For adult patients, common dosages have included 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, and 600 mg. These doses are often taken orally once daily (q.d.) or twice daily (BID), sometimes on specific days of the week (e.g., 3 days a week) or in cycles (e.g., 21 days out of 4 weeks).

For pediatric patients or those undergoing transplant, vorinostat has been studied at doses based on body surface area, such as 60 milligrams per square meter (mg/m2) twice daily, with a maximum dose of 100 mg twice daily. This regimen, totaling 120 mg/m2/day, has been explored in transplant recipients from day -10 to day 30 post-transplant. Other investigational doses in pediatric trials include 180 mg/m2 and 230 mg/m2.

Vorinostat is frequently studied in combination with other drugs, and its dose may be adjusted when used as part of a multi-drug regimen. Examples include combinations with pembrolizumab (e.g., 100 mg or 200 mg vorinostat), erlotinib (e.g., 200 mg to 400 mg vorinostat), bortezomib (e.g., 200 mg to 400 mg vorinostat), and lenalidomide (e.g., 300 mg to 400 mg vorinostat).

Side Effects

In clinical trials, patients taking Vorinostat experienced certain side effects more often than those on placebo. The most common side effect was nausea, affecting 55.5% of patients on Vorinostat compared to 35.2% on placebo. Other common side effects included:

• Diarrhea: 48.0% of patients on Vorinostat experienced diarrhea, compared to 29.1% on placebo.
• Fatigue: 43.7% of patients on Vorinostat experienced fatigue, compared to 34.9% on placebo.
• Vomiting: 39.3% of patients on Vorinostat experienced vomiting, compared to 19.1% on placebo.
• Neutropenia (low white blood cell count): 37.6% of patients on Vorinostat experienced neutropenia, compared to 33.8% on placebo.
• Thrombocytopenia (low platelet count): 31.1% of patients on Vorinostat experienced thrombocytopenia, compared to 16.9% on placebo.
• Decreased appetite: 27.6% of patients on Vorinostat experienced decreased appetite, compared to 22.4% on placebo.
• Anemia (low red blood cell count): 25.4% of patients on Vorinostat experienced anemia, compared to 19.1% on placebo.

Some side effects occurred at similar rates in both Vorinostat and placebo groups, such as constipation (24.0% on Vorinostat vs 24.1% on placebo), cough (18.9% vs 18.0%), and dyspnoea (18.8% vs 18.9%).

Clinical Trial Results

Advanced Solid Tumors (NCT00106626)

A Phase 1 study investigated Vorinostat, also known as suberoylanilide hydroxamic acid, in patients with advanced solid tumors. The study aimed to determine the maximum tolerated dose (MTD) by observing dose-limiting toxicities (DLTs), which were reported across various dose levels and schedules.

The study also tracked disease progression in different treatment groups combining Vorinostat with pemetrexed and cisplatin:

• In the cohort receiving Vorinostat twice daily plus pemetrexed and cisplatin, 4 participants experienced disease progression.
• In the cohort receiving Vorinostat once daily plus pemetrexed and cisplatin, 1 participant experienced disease progression.
• In cohorts receiving Vorinostat twice daily or once daily with pemetrexed alone, 9 and 10 participants, respectively, experienced disease progression.

Multiple Myeloma (NCT00111813)

A Phase 1 study evaluated Vorinostat in combination with bortezomib for patients with multiple myeloma. The mean duration of treatment varied across different regimens, with some participants treated for an average of 107.1 days, while others had shorter durations.

Dose modifications due to adverse experiences were observed. For example, the mean time to the first dose modification ranged from 32 days (for Vorinostat 400 mg + bortezomib 1.3 mg/m² group) to 128 days (for Vorinostat 400 mg + bortezomib 1.1 mg/m² group).

Metastatic or Unresectable Melanoma (NCT00121225)

In a study of Vorinostat for patients with metastatic or unresectable melanoma, 2 participants in Arm I showed an objective response to treatment, as assessed by RECIST (Response Evaluation Criteria for Solid Tumors). The median time until disease progression for patients on Vorinostat was 4 months.

Cutaneous T-Cell Lymphoma (NCT00127101)

A terminated investigational study explored Vorinostat with Targretin in patients with cutaneous T-cell lymphoma. This study also aimed to determine the maximum tolerated dose, with dose-limiting toxicities reported. The number of participants who responded to treatment varied by cohort:

• 3 participants responded in Cohort 1.
• 5 participants responded in Cohort 2.
• 3 participants responded in Cohort 2a.
• 1 participant responded in Cohort 2b.
• 3 participants responded in Cohort 6.
• 1 participant responded in Cohort 7.

Solid Tumors (Pharmacokinetics and Safety) (NCT00127127)

This study investigated the pharmacokinetics (how the body handles the drug) and safety of Vorinostat in patients with solid tumors at different oral doses (100 mg, 200 mg, 400 mg, 500 mg).

Key safety findings included:

Vorinostat is currently being investigated in a variety of clinical trials, exploring its potential to treat conditions ranging from rare genetic disorders to various cancers and HIV. These studies aim to understand how safe and effective Vorinostat can be, often in combination with other therapies.

• An exploratory Phase 1 study, "An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Pitt Hopkins Syndrome," is recruiting 5 participants with Pitt Hopkins Syndrome. Sponsored by Unravel Biosciences, Inc., this study uses an N-of-1 design where each patient serves as their own control, evaluating low and high doses of Vorinostat alongside a placebo phase.
• Also sponsored by Unravel Biosciences, Inc., the "Rett REVOLUTION Trial: An Exploratory Evaluation of the Safety and Efficacy of Vorinostat in Rett Syndrome" is a Phase 1, placebo-controlled, single-blinded study for 15 individuals with Rett Syndrome. Similar to the Pitt Hopkins trial, patients act as their own controls to assess the safety and efficacy of Vorinostat at different dose levels.
• The University of Minnesota is sponsoring "A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST]." This Early Phase 1 study plans to enroll 8 participants with newly diagnosed malignant peripheral nerve sheath tumors (MPNSTs), testing a short course of mirdametinib plus Vorinostat before standard care.
• For individuals with HIV, the University of North Carolina, Chapel Hill, is conducting "The DART DELIVER-02 Study," a Phase 1 trial with an enrollment target of 24. This study evaluates the safety and tolerability of experimental antibodies MGD014 and MGD020, with one arm specifically including Vorinostat.
• The Fred Hutchinson Cancer Center is sponsoring a Phase 2 trial, "Vorinostat and 177Lu-PSMA-617 for the Treatment of PSMA-Low Metastatic Castration-Resistant Prostate Cancer," aiming for 15 participants. This study investigates Vorinostat in combination with 177Lu-PSMA-617 for metastatic castration-resistant prostate cancer that has low levels of prostate-specific membrane antigen (PSMA).
• In the field of leukemia, "TINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia II" is a Phase 1/Phase 2 study led by Tanja Andrea Gruber, targeting 90 participants. This trial seeks to improve treatment for infants with acute lymphoblastic leukemia by testing the immunotherapy blinatumomab to clear persistent leukemia.
• The Medical College of Wisconsin is conducting "Venetoclax to Augment Epigenetic Modification and Chemotherapy," a Phase 1 study enrolling 40 patients with relapsed or refractory acute myeloid leukemia. This research tests the addition of venetoclax to 5-azacitidine and Vorinostat, followed by standard chemotherapy.
• For Crohn's disease, the National Institute of Allergy and Infectious Diseases (NIAID) is sponsoring "An Open-Label, Proof of Consent Study of Vorinostat for the Treatment of Mdoerate-to-Severe Crohn s Disease and Maintenance Therapy With Ustekinumab," a Phase 1/Phase 2 trial with 35 participants. This study aims to assess the safety and effectiveness of Vorinostat for moderate-to-severe Crohn's disease, with maintenance therapy using ustekinumab.
• New York Medical College is leading "Vorinostat in Combination With Chemotherapy in Relapsed/Refractory Solid Tumors and CNS Malignancies," a Phase 1 study for 30 participants with various relapsed/refractory solid tumors and CNS malignancies. Investigators are testing Vorinostat in combination with vincristine, irinotecan, and temozolomide.
• Finally, "Pediatric Precision Laboratory Advanced Neuroblastoma Therapy" is a Phase 2 study sponsored by Giselle Sholler, targeting 500 participants with neuroblastoma. This multicenter study evaluates molecularly guided therapy combined with standard immunotherapy, with or without DFMO.

Where to Participate

Clinical trials involving Vorinostat are accessible across a wide geographic area, with study sites located in 26 states, covering 39 cities and a total of 45 individual locations. This broad reach helps ensure that patients in various regions may have the opportunity to participate.

The cities with the most active recruiting sites include:

• Minneapolis, Minnesota (3 sites)
• Little Rock, Arkansas (2 sites)
• Charlotte, North Carolina (2 sites)
• Orlando, Florida (2 sites)
• Hershey, Pennsylvania (2 sites)
• San Diego, California (2 sites)
• Portland, Oregon (2 sites)

Eligibility for these trials generally includes individuals between the ages of 1 and 65 years, with all genders welcome to participate. It is important to note that these studies do not typically enroll healthy volunteers, focusing instead on patients with specific medical conditions.

Development Timeline

The journey of Vorinostat in clinical research began on January 27, 2003, with the latest trial starting on December 3, 2025. Over this period, a substantial research effort has led to a total of 272 clinical trials, enrolling more than 17,692 participants.

Early development primarily focused on Phase 1 and Phase 2 studies, with 108 Phase 1 trials, 86 Phase 2 trials, and 59 Phase 1/Phase 2 trials conducted. While the majority of research remains in these early stages, 6 Phase 3 trials have also been initiated, indicating progression to later-stage evaluation.

Key organizations have driven much of this research. The National Cancer Institute (NCI) has sponsored the most trials, with 63 studies, followed by Merck Sharp & Dohme LLC with 27, and M.D. Anderson Cancer Center with 19. Other significant contributors include the University of Washington, Fred Hutchinson Cancer Center, and the University of North Carolina, Chapel Hill.

The range of conditions studied for Vorinostat has expanded significantly since its initial investigations into IBS-C and hyperphosphatemia. The drug's potential has been explored across a broad spectrum of cancers, including various types of acute myeloid leukemia, breast cancer, neuroblastoma, lymphomas, and prostate cancer. More recently, its application has broadened to include rare genetic disorders like Pitt Hopkins Syndrome and Rett Syndrome, as well as infectious diseases such as HIV and inflammatory conditions like Crohn's disease, showcasing a diverse and evolving pipeline.