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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Study Summary

This trial is testing a new combination therapy for metastatic uveal melanoma to see if it can make tumors shrink or stop growing.

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.Check my eligibility

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.See study design

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.

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

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Overall Response Rate

Secondary outcome measures

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%

Oedema peripheral

16%

Stomatitis

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%

Vitreous floaters

11%

Pollakiuria

11%

Dyspepsia

11%

Hypoalbuminaemia

11%

Hypertension

11%

Tumour Pain

Hypokalaemia

Weight decreased

Macular oedema

Rhinitis allergic

Iron deficiency

Infusion related reaction

Hypertrichosis

Nasopharyngitis

Proteinuria

Visual impairment

Flank pain

Rash

Pruritus

Pain in extremity

Blood bilirubin increased

Rhinnorrhoea

Hypotension

Musculoskeletal pain

Pleural effusion

Restless legs syndrome

Chorioretinopathy

Trichomegaly

Rectal haemorrhage

Hypocalcaemia

Nail disorder

Pruritus generalised

Musculoskeletal chest pain

Hypophosphataemia

Nervous system disorder

Colitis

Abdominal pain lower

Urinary incontinence

Infection

Wound

Bone pain

Ascites

Anal haemorrhage

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

Device occlusion

Large intestine perforation

Confusional state

Upper respiratory tract infection

Skin papilloma

Streptococcal infection

Large intestinal ulcer

Cholangitis

Large intestinal ulcer hemorrhage

Kidney infection

Back pain

Alopecia

Urinary tract infection bacterial

Bacterial sepsis

Hyperkeratosis

Rhabdomyolysis

Tumour pain

Melanocytic naevus

Rectal hemorrhage

Urinary tract obstruction

Epistaxis

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

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

Binimetinib

2018

Completed Phase 3

~1100

Belinostat

2006

Completed Phase 2

~430

0 / 4Eligibility 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.