Vorinostat for Uveal Melanoma

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: HDAC inhibitors, Warfarin

Disqualifiers: Brain metastases, Second malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks per course, repeating

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how well a medication called vorinostat treats eye melanoma that has spread to other parts of the body. Vorinostat may block enzymes that help tumor cells grow. The study seeks individuals diagnosed with metastatic uveal melanoma who show noticeable disease progression. Participants will take vorinostat in cycles, with breaks in between, as long as the treatment remains safe and effective. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop taking my current medications for the trial?

The trial requires a 14-day period without taking HDAC inhibitors or similar compounds before starting. If you're on warfarin, you may need to switch to another medication. The protocol doesn't specify other medication restrictions, so check with the trial team for details.

Is there any evidence suggesting that vorinostat is likely to be safe for humans?

Research has shown that vorinostat, a treatment under study for metastatic eye melanoma, was tested in earlier studies. Some patients experienced side effects, including fatigue, nausea, low white blood cell counts, and high blood sugar levels. These side effects were noticeable and impacted patients.

Vorinostat is still under investigation and has not yet received approval for this specific type of melanoma. As it is in a Phase 2 trial, some basic safety information is available, but more research is needed to fully understand its tolerability. Prospective trial participants should consult a healthcare provider to discuss potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vorinostat is unique because it targets uveal melanoma by modulating gene expression. Unlike traditional treatments like surgery, radiation, or chemotherapy, vorinostat is an oral medication that influences the acetylation of histones, potentially halting cancer cell growth and survival. Researchers are excited about vorinostat because it offers a novel mechanism of action, which might provide a new avenue for tackling this challenging cancer, especially for patients whose disease has progressed beyond the reach of conventional therapies.

What evidence suggests that vorinostat might be an effective treatment for uveal melanoma?

Research has shown that vorinostat, the treatment being tested in this trial, might help treat eye melanoma, especially when it has spread to other parts of the body. Vorinostat blocks certain proteins that cancer cells need to grow. Studies have found that vorinostat can sometimes shrink tumors and help keep the disease stable in some patients. However, it did not achieve the main goal of significantly shrinking tumors in past trials. Overall, early evidence suggests it might help slow the disease's progress. ^{1 2 3 4 6}

Who Is on the Research Team?

Alexander N Shoushtari

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Adults with metastatic uveal melanoma (eye melanoma that has spread) can join this trial. They must have measurable disease, acceptable organ function tests, and a life expectancy over 3 months. Participants need to agree to use contraception and cannot be pregnant or breastfeeding. Those with certain serious health conditions or taking specific medications are excluded.

Inclusion Criteria

You have a low level of white blood cells.

You need to have a certain number of a type of white blood cell called neutrophils in your blood.

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

Patients who are receiving any other investigational agents

No concomitant anti-cancer chemotherapy or other systemic drugs. Palliative radiation therapy will be allowed as long as the patient meets all other eligibility criteria

You have tried other treatments before. You need to wait at least 3 weeks after your last treatment, and 6 weeks if the last treatment included specific drugs. Your doctor thinks your disease got worse after the last treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vorinostat orally twice daily for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

4 weeks per course, repeating

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vorinostat

Trial Overview The trial is testing Vorinostat's effectiveness in treating metastatic uveal melanoma by inhibiting enzymes needed for tumor cell growth. It includes laboratory biomarker analysis to monitor the response and requires prior progression on other therapies.

How Is the Trial Designed?

Group I: Treatment (vorinostat) Experimental Treatment 2 Interventions

Patients receive vorinostat PO BID for 3 days weekly for 4 weeks. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Vorinostat is already approved in United States, European Union for the following indications:

Approved in United States as Zolinza for:

• Cutaneous T-cell lymphoma

Approved in European Union as Zolinza for:

• Cutaneous T-cell lymphoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Institut Curie Paris

Collaborator

Trials

1

Recruited

40+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Moffitt Cancer Center P2C

Collaborator

Trials

1

Recruited

40+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01587352

Vorinostat in Treating Patients With Metastatic Melanoma ... This phase II trial studies how well vorinostat works in treating patients with melanoma of the eye that has spread to other parts of the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8998190/

Histone Deacetylase (HDAC) Inhibitors: A Promising ... A variety of HDAC inhibitors (HDACi) have been developed and evaluated in multiple solid and hematologic malignancies, showing promising results.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00121225?cond=%22Melanoma,%20Uveal%22&intr=%22Histone%20Deacetylase%20Inhibitors%22&viewType=Table&rank=5

Vorinostat in Treating Patients With Metastatic or ... Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Detailed ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/24464266/

Phase II trial of vorinostat in advanced melanoma - PubMed Vorinostat demonstrated some early responses and a high proportion of patients with stable disease, but did not meet its primary endpoint of response.

5. researchgate.net researchgate.net/publication/259918778_Phase_II_trial_of_vorinostat_in_advanced_melanoma

Phase II trial of vorinostat in advanced melanoma In a phase II clinical trial, vorinostat (suberoyl-anilide-hydroxamic acid: SAHA) demonstrated some early responses in patients with advanced CM ...

6. mdpi.com mdpi.com/1422-0067/23/16/9378

Evaluation of the Therapeutic Potential of Histone ... This review discusses (1) what is known about HDAC6i in MUM and (2) whether HDAC6 inhibitors offer a potential therapeutic option for MUM.