What side effects are associated with this type of intervention?

Common treatments for uveal melanoma, such as Binimetinib (a MEK inhibitor) and Belinostat (an HDAC inhibitor), have notable ocular side effects. Binimetinib can cause dose-related retinal lesions, serous neuroretinal detachments, and edema, which typically decrease over time without lasting functional deficits. Belinostat may lead to corneal ulcers, blurred vision, and dry eye, with most cases being reversible through dose modification or delay. Patients undergoing these treatments should be closely monitored for ocular toxicity, and management strategies should be individualized based on the severity of symptoms.

What prior FDA approvals exist?

As of now, there are no specific FDA approvals for the treatment of Uveal Melanoma using MEK inhibitors like Binimetinib or HDAC inhibitors like Belinostat. The current research is investigating the efficacy of these drugs in combination for metastatic uveal melanoma, aiming to determine if they can shrink or halt tumor growth. This indicates that while these drugs are being studied, they have not yet received FDA approval for this specific indication.

What other types of research exist?

Promising novel alternatives for Uveal Melanoma treatment in 2024 include Tebentafusp, an immunotherapy that has shown efficacy in clinical trials, and Selpercatinib, a selective RET inhibitor that has demonstrated activity in RET-altered cancers. Additionally, ongoing research into combination therapies involving immune checkpoint inhibitors like Nivolumab and Ipilimumab may offer new options.

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Histone Deacetylase Inhibitor

Binimetinib + Belinostat for Uveal Melanoma

Phase 2

Recruiting

Led By Ahmad Tarhini, MD, PhD

Research Sponsored by H. Lee Moffitt Cancer Center and Research Institute

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have metastatic uveal melanoma, either initial presentation or recurrent, that is histologically diagnosed

Male or female, aged >/= 18 years old

Must not have

Participants with clinically significant cardiovascular or cerebrovascular disease: History of cerebrovascular accident or transient ischemic attack within past 6 months, Uncontrolled hypertension, Myocardial infarction, CABG or unstable angina within the past 6 Months, New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months, Clinically significant peripheral vascular disease within past 6 months, Pulmonary embolism, DVT, or other thromboembolic event within past 6 months, PT INR >1.5 unless the patient is on full-dose warfarin

Participants must not have an active infection requiring current treatment with parenteral antibiotics

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, Binimetinib and Belinostat, in people with a type of eye cancer that has spread. The goal is to see if these drugs can stop the cancer from growing or make it shrink.

Who is the study for?

Adults over 18 with metastatic uveal melanoma can join this trial. They should have a life expectancy of more than 3 months, measurable disease, and normal organ/marrow function. Participants must not have had MEK or HDAC inhibitors before and should be free from active brain metastases. Contraception is required during the study.

What is being tested?

The trial is testing a combination of two drugs, Binimetinib and Belinostat, to see if they can shrink or halt the growth of tumors in patients with metastatic uveal melanoma.

What are the potential side effects?

Possible side effects may include fatigue, nausea, skin rash, changes in blood pressure or heart rhythm disturbances due to Binimetinib; and fatigue, nausea, vomiting, diarrhea due to Belinostat. Each patient's experience may vary.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with metastatic uveal melanoma.

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I am 18 years old or older.

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I am fully active or can carry out light work.

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My blood counts and organ functions are within normal ranges.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had serious heart or blood vessel problems in the last 6 months.

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I am not currently on IV antibiotics for an infection.

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I have had serious eye conditions not fixed by treatment.

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I have taken steroids for lung inflammation or ILD.

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I haven't had any new drug trials or radiation for my eye melanoma in the last 4 weeks.

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I can take pills and do not have major stomach or intestine problems affecting drug absorption.

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I had major surgery over 4 weeks ago and have recovered without any significant infections.

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I have a serious or non-healing wound, ulcer, or bone fracture.

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My heart is healthy with no recent major issues.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Response Rate

Secondary study objectives

Overall Survival

Progression Free Survival

Side effects data

From 2022 Phase 3 trial • 702 Patients • NCT02928224

78%

Diarrhoea

68%

Dermatitis acneiform

59%

Nausea

54%

Fatigue

51%

Vomiting

51%

Dry Skin

43%

Pyrexia

43%

Anaemia

41%

Decreased appetite

38%

Abdominal pain

38%

Constipation

35%

Dyspnoea

32%

Vision blurred

30%

Blood creatine increased

30%

Blood creatine phosphokinase increased

24%

Arthralgia

24%

Myalgia

24%

Skin fissures

22%

Back Pain

22%

Dizziness

19%

Malaise

19%

Urinary tract infection

19%

Headache

19%

Aspartate aminotransferase increased

16%

Asthenia

16%

Stomatitis

16%

Oedema peripheral

16%

PPE syndrome

16%

Hypomagnesaemia

16%

Rash maculo-papular

16%

Palmar-planar erythrodysaesthesia

16%

Chills

16%

Paronychia

16%

Rash pustular

16%

Alanine aminotransferase increased

16%

Dysgeusia

16%

Peripheral sensory neuropathy

14%

Cough

14%

Abdominal pain upper

14%

Infusion-related reaction

14%

Ejection fraction decreased

14%

Dry eye

11%

Trichiasis

11%

Pollakiuria

11%

Vitreous floaters

11%

Dyspepsia

11%

Hypoalbuminaemia

11%

Hypertension

11%

Tumour Pain

Rhinitis allergic

Infusion related reaction

Hypokalaemia

Visual impairment

Macular oedema

Hypertrichosis

Iron deficiency

Nasopharyngitis

Weight decreased

Flank pain

Proteinuria

Rash

Pruritus

Pain in extremity

Blood bilirubin increased

Rhinnorrhoea

Hypotension

Pleural effusion

Restless legs syndrome

Musculoskeletal pain

Nervous system disorder

Wound

Trichomegaly

Infection

Hypocalcaemia

Hypophosphataemia

Rectal haemorrhage

Anal haemorrhage

Ascites

Colitis

Abdominal pain lower

Nail disorder

Pruritus generalised

Bone pain

Musculoskeletal chest pain

Chorioretinopathy

Urinary incontinence

Insomnia

Gastroesophageal reflux disease

Abdominal distension

Eczema

Cystitis

Renal failure

Conjunctivitis

Syncope

Dehydration

Dry Mouth

Skin hyperpigmentation

Muscle spasms

Erythema

Retinal detachment

Pulmonary embolism

Dysphonia

Haematuria

Blood creatinine increased

Depression

Palpitations

Tumour pain

Large intestinal ulcer hemorrhage

Melanocytic naevus

Urinary tract infection bacterial

Large intestinal ulcer

Kidney infection

Epistaxis

Hyperkeratosis

Rectal hemorrhage

Streptococcal infection

Alopecia

Upper respiratory tract infection

Skin papilloma

Large intestine perforation

Bacterial sepsis

Cholangitis

Urinary tract obstruction

Confusional state

Device occlusion

Back pain

Rhabdomyolysis

Colon cancer

Sepsis

Acute kidney injury

Large intestine ulcer

Neutropenia

Bacteria sepsis

Hydronephrosis

Neuropathy peripheral

Abdominal abscess

Hyperglycaemia

100%

80%

60%

40%

20%

Study treatment Arm

Combined Safety Lead-in

Phase 3: Triplet Arm

Phase 3: Doublet Arm

Phase 3: Control Arm

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Binimetinib + BelinostatExperimental Treatment2 Interventions

Participants will receive binimetinib by mouth two times a day, every day during each cycle. Each cycle will last for 21 days. Participants will receive belinostat by intravenous infusion on days 1 through 5 of each cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Belinostat

2006

Completed Phase 2

~430

Binimetinib

2018

Completed Phase 3

~1250

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Uveal Melanoma treatments often target specific pathways involved in tumor growth and survival. Binimetinib, a MEK inhibitor, works by blocking the MEK enzyme, which is part of the MAPK/ERK pathway that promotes cell division and survival. By inhibiting this pathway, Binimetinib can reduce tumor growth and proliferation. Belinostat, an HDAC inhibitor, interferes with histone deacetylases, enzymes that modify proteins associated with DNA, leading to changes in gene expression that can induce cancer cell death and inhibit tumor growth. These mechanisms are crucial for Uveal Melanoma patients as they offer targeted approaches to disrupt cancer cell function and potentially improve treatment outcomes.