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Kinase Inhibitor

Encorafenib + Binimetinib Before Surgery for Melanoma

Phase 2

Waitlist Available

Led By Leslie A Fecher

Research Sponsored by ECOG-ACRIN Cancer Research Group

Eligibility Criteria Checklist

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

Must have

Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1

Patient must be able to take oral medications

Must not have

Patient must not have any concurrent neuromuscular disorder that is associated with elevated creatine kinase (CK)

Patient must not have any evidence of distant metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

All Individual Drugs Already Approved

Approved for 5 Other Conditions

Summary

This trial is studying a combination of two drugs, encorafenib and binimetinib, to see how well they work before surgery in treating patients with melanoma that has spread to the lymph nodes and has a BRAF V600 mutation. 18F-FLT PET/CT scans may be used to predict how well the melanoma will respond to the treatment.

Who is the study for?

This trial is for adults with stage IIIB-D melanoma that has spread to lymph nodes and have a BRAF V600 mutation. They must be able to take oral meds, lie still for PET/CT scans, use contraception if of childbearing potential, and not have distant metastases or other serious health issues. HIV-positive patients can join if their condition is stable.

What is being tested?

The effectiveness of Encorafenib and Binimetinib before surgery in treating melanoma with lymph node involvement is being tested. The study also evaluates how well an imaging agent (18F-FLT) used in PET/CT scans predicts the response to these drugs.

What are the potential side effects?

Potential side effects include risk of heart problems, bleeding events, liver function changes, high blood pressure, fatigue, skin rash or disorders, vision changes like retinal vein occlusion (RVO), muscle pain or weakness due to elevated creatine kinase (CK).

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or restricted in physically strenuous activity but can do light work.

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I can take pills by mouth.

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My scans show measurable cancer, taken within the last 4 weeks.

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My melanoma is stage III B/C/D and can be seen or felt.

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My melanoma can be entirely removed by surgery, as confirmed by a specialist.

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I have at least one visible lymph node metastasis, but not in the N1c category.

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My cancer has a BRAF V600 mutation.

Exclusion Criteria

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

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I do not have a muscle disorder that increases my CK levels.

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My cancer has not spread to distant parts of my body.

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I do not have an infection that needs treatment with IV antibiotics.

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I have no history or current signs of retinal vein occlusion.

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I have never had pancreatitis.

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My heart is healthy and I don't have significant heart disease.

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I have not had radiation on the area where my disease can be measured.

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My digestive system works well enough to absorb medication properly.

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I do not have active hepatitis B or C.

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I have never been treated with BRAF or MEK inhibitors.

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I am not pregnant or breastfeeding.

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I am not allergic to binimetinib or encorafenib.

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

Change in fluorothymidine F-18 (18F-FLT) positron emission tomography (PET)/computed tomography (CT) uptake

Pathologic complete response (pCR) rate

Secondary study objectives

Change in 18F-FLT PET/CT uptake

Change in CD8 positive (+) tumor infiltrating lymphocytes

Change in CD8+ T cell infiltration in tumor or tumor bed

+7 more

Other study objectives

Change in Ki-67 status in tumor or tumor bed

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

Hypokalaemia

Visual impairment

Infusion related reaction

Macular oedema

Hypertrichosis

Iron deficiency

Nasopharyngitis

Weight decreased

Flank pain

Proteinuria

Rash

Pruritus

Pain in extremity

Blood bilirubin increased

Rhinnorrhoea

Hypotension

Restless legs syndrome

Nervous system disorder

Wound

Trichomegaly

Infection

Pleural effusion

Hypocalcaemia

Hypophosphataemia

Rectal haemorrhage

Musculoskeletal pain

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

Melanocytic naevus

Large intestinal ulcer

Tumour pain

Kidney infection

Large intestinal ulcer hemorrhage

Urinary tract infection bacterial

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.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (18F-FLT, PET/CT, encorafenib, binimetinib, surgery)Experimental Treatment6 Interventions

NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Binimetinib

FDA approved

Computed Tomography

2017

Completed Phase 2

~2740

Conventional Surgery

2006