Melanoma of Unknown PrimaryPhase 2NCT04221438
Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement
A Phase 2 study testing Binimetinib, Conventional Surgery and Encorafenib in people with Melanoma of Unknown Primary and Metastatic Malignant Neoplasm in Lymph Node, run by ECOG-ACRIN Cancer Research Group at 10 sites in United States.
Trial summary
This phase II trial studies how well encorafenib and binimetinib work before surgery in treating patients with BRAF V600-mutated stage IIIB-D melanoma that has spread to the lymph nodes. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma of Unknown Primary, Metastatic Malignant Neoplasm in Lymph Node, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8
- What is being tested?
- Binimetinib, Conventional Surgery and Encorafenib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 10 sitesUnited States
- Study dates
- 22 Sep 2021to 31 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient must have histologically proven melanoma that is clinically evident (macroscopic lymphadenectomy [LAD]) stage III B/C/D, (American Joint Committee on Cancer [AJCC] 8th edition) of cutaneous origin or unknown primary. Patients must have at least one clinically evident lymph node metastasis (N1c patients are not eligible).
- This may be an initial presentation with primary tumor and nodal metastases or locoregional nodal relapse with history of resected primary melanoma
- Stage IIIB
- T0-3a N1b M0
- T1a-3a N2b M0
- Stage IIIC
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- T0 or T3b-4b N2b M0
- T3b-4b N1b M0
- Any T N2c M0 (at least 1 clinically evident node)
- T0-4a N3b M0
- Stage IIID
- T4b N3b/c M0 (if 3c: at least 1 clinically evident node)
- Patient must have measurable disease on baseline imaging scans, obtained within 4 weeks prior to registration as defined by RECIST and by the following criteria
- The melanoma target tumor must be completely resectable as determined by a surgical oncologist or experienced melanoma surgeon
- Extensive satellitosis or in transit metastases are not considered completely resectable
- Patient must have BRAF V600 mutation positive based on report from Clinical Laboratory Improvement Act (CLIA) certified laboratory
- Patient must be medically fit to undergo surgery
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained < 14 days prior to registration)
- Hemoglobin >= 8 g/dL without transfusion (obtained < 14 days prior to registration)
- Platelets >= 100 x 10^9/L without transfusion (obtained < 14 days prior to registration)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.0 x upper limit of normal (ULN) (obtained < 14 days prior to registration)
- Total bilirubin =< 1.5 x ULN and < 2 mg/dL; OR total bilirubin > 1.5 x ULN with indirect bilirubin < 1.5 x ULN (obtained < 14 days prior to registration)
- Serum creatinine =< 1.5 x ULN, or calculated creatinine clearance > 50 mL/min by Cockcroft-Gault formula (obtained < 14 days prior to registration)
- Prothrombin time (PT), international normalized ratio (INR), and partial thromboplastin time (PTT) =< 1.5 x ULN (obtained < 14 days prior to registration)
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patient must be able to take oral medications
- Patient must be able to lie still during the 18F-FLT PET/CT scan for the duration of the imaging study (up to 1.5 hours), have no previous indication of allergic reaction to the radiotracer, and meet the size limits of the qualified PET/CT scanner
- Patient must be participating in this study at an institution which has completed the ECOG-American College of Radiology Imaging Network (ACRIN) defined PET/CT scanner qualification procedures and received ECOG-ACRIN PET scanner approval
- Patients known to be human immunodeficiency virus (HIV) positive are eligible if they have undetectable HIV viral load and stable and adequate CD4 counts (>= 500 mm^3) on screening labs provided they meet all other protocol criteria for participation and that there is no high risk drug interactions
- Women of childbearing potential and sexually active males must use accepted and effective method(s) of contraception or to abstain from sexual intercourse for the duration of their participation in the study and for at least 30 days after the last dose of protocol treatment for female patients, and for at least 90 days after the last dose of protocol treatment for male patients. In addition, female patients must not donate ova from the time of registration until 30 days after the last dose of study treatment. Male patients must not donate sperm from the time of registration until 90 days after the last dose of protocol treatment
- Patient may be on anticoagulation at prophylactic or therapeutic levels. Patients must not be using anticoagulants at therapeutic levels that may interfere with encorafenib and binimetinib
Who cannot join
- Stage IV melanoma
- Patient must not have any prior treatment with BRAF inhibitor (BRAFi) or MEK inhibitor (MEKi)
- Patient must not have any evidence of distant metastases
- Patient must not have any prior adjuvant therapy at this disease presentation; prior immune therapy (such as adjuvant interferon or checkpoint inhibitors) is permitted if >= 6 months from last treatment
- Patient must not have any prior radiation to the site of evaluable disease
- Patient must not have active infection requiring treatment with parenteral antibiotics
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- Patient must not have active hepatitis B, and/or active hepatitis C infection given concerns for drug interactions or increased toxicities. Testing is not required
- Patient must not have other significant medical, surgical, or psychiatric conditions that in the opinion of the investigator may interfere with compliance, make the administration of study medications hazardous
- Patient must not have had previous or concurrent other malignancy with the following exceptions:
- Adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix
- Other solid tumor: if treated and without evidence of recurrence for at least 2 years prior to study entry
- Women must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the systemic antineoplastic medications, as well as surgery and radiation being used. Patients must also not expect to conceive or father children from the time of registration, while on study, treatment, and until at least 30 days after the last dose of study treatment (for female patients) and 90 days after the last dose of study treatment (for male patients). All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
- Patient must not have known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
- Patient must not have impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
- History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) < 6 months prior to registration
- Congestive heart failure requiring treatment (New York Heart Association grade >= 2)
- Left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
- Uncontrolled hypertension defined as persistent systolic blood pressure >= 150 mmHg or diastolic blood pressure >= 100 mmHg despite current therapy
- History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)
- Baseline corrected QT (QTc) interval >= 480 ms
- Patient must not have impairment of gastrointestinal function or disease which may significantly alter the absorption of study drug (e.g., active ulcerative disease, uncontrolled vomiting or diarrhea, malabsorption syndrome, small bowel resection with decreased intestinal absorption), or recent (=< 3 months) history of a partial or complete bowel obstruction, or other conditions that will interfere significantly with the absorption of oral drugs
- Patient must not have any known history of acute or chronic pancreatitis
- Patient must not have any concurrent neuromuscular disorder that is associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy
- Patient must not have any known history or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity, factor V Leiden or activated protein C resistance); history of retinal degenerative disease
- Patient must not use any medication (including herbal medications, supplements, or foods), or use of a prohibited medication =< 1 week prior to registration
- Patient must not have a history of thromboembolic or cerebrovascular events =< 12 weeks prior to registration. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli
- NOTE: Patients with thromboembolic events related to indwelling catheters or other procedures may be registered
- NOTE: Patients with either deep vein thrombosis or pulmonary emboli that does not result in hemodynamic instability are allowed to register as long as they are on a stable dose of anticoagulants for at least 4 weeks
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Los Angeles County-USC Medical Center
Los Angeles, California, 90033
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Siteman Cancer Center at Christian Hospital
St Louis, Missouri, 63136
About this study
Official title: A Phase II Neoadjuvant Study of Encorafenib With Binimetinib in Patients With Resectable Locoregional Metastases From Cutaneous or Unknown Primary Melanoma (Stages III N1B/C/D)
This phase II trial studies how well encorafenib and binimetinib work before surgery in treating patients with BRAF V600-mutated stage IIIB-D melanoma that has spread to the lymph nodes. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial also studies how well 18F-FLT positron emission tomography (PET)/computed tomography (CT) works in predicting the response of melanoma to encorafenib and binimetinib. 18F-FLT is an imaging agent, sometimes called a tracer. PET and CT are types of imaging scans. Using 18F-FLT PET/CT together with encorafenib and binimetinib may provide more information on melanoma over time.
Read the detailed description
PRIMARY CLINICAL OBJECTIVE:
- To evaluate the pathologic complete response (pCR) rate of neoadjuvant treatment with encorafenib and binimetinib.
SECONDARY CLINICAL OBJECTIVES:
- To determine response rate (RR) (Response Evaluation Criteria in Solid Tumors [RECIST]), disease-free survival (DFS) and overall survival (OS).
II. To describe correlation of pCR with RR, DFS and OS. III. To assess safety and toxicity.
CORRELATIVE SCIENCE OBJECTIVES:
- To evaluate CD8 positive (+) T cell infiltration and Ki-67 status in tumor or tumor bed pre, during, and post neoadjuvant treatment and the change in CD8+ tumor infiltrating lymphocyte (TIL) with neoadjuvant treatment and correlate with clinical response.
II. To compare local review for pathologic response with central pathology review.
III. To assess the correlation between change in fluorothymidine F-18 (18F-FLT) PET/CT uptake and change in Ki-67.
IMAGING OBJECTIVES:
- To compare the change in 18F-FLT PET/CT uptake (from baseline to post-neoadjuvant therapy) among patients with and without pathologic complete response.
II. To compare post-neoadjuvant 18F-FLT PET/CT uptake among patients with and without pathologic complete response.
III. To estimate an optimal threshold for prediction of pathologic complete response using i) change in 18F-FLT PET/CT uptake, and ii) post-neoadjuvant 18F-FLT PET/CT uptake.
IV. To assess the correlation between change in 18F-FLT PET/CT uptake and change in Ki-67.
OUTLINE:
NEOADJUVANT TREATMENT: Patients receive 18F-FLT intravenously (IV) and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (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.
After completion of study treatment, patients are followed up every 3 months for 1 year, then every 6 months for 3 years.
- Conditions
- Melanoma of Unknown Primary, Metastatic Malignant Neoplasm in Lymph Node, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIC Cutaneous Melanoma AJCC v8, Pathologic Stage IIID Cutaneous Melanoma AJCC v8, Recurrent Cutaneous Melanoma
- Being tested
- Binimetinib, Conventional Surgery, Encorafenib, Fluorothymidine F-18
- Medical subject headings
- Lymphatic Metastasis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BinimetinibDrug
Also called NSC 788187, ARRY-438162, MEK162, Mektovi
Given PO
Conventional SurgeryProcedure or surgery
Undergo surgery
EncorafenibDrug
Also called ONO-7702, LGX818
Given PO
Fluorothymidine F-18Other
Also called 18F-FLT, 3'-deoxy-3'- 18F fluorothymidine, FLT
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib | Experimental | 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. Receives: Drug: Binimetinib; Procedure: Conventional Surgery; Drug: Encorafenib; Other: Fluorothymidine F-18 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathologic Complete Response
Pathologic complete response (pCR) is defined as complete absence of viable tumor in the treated tumor bed. Partial pathologic response (pPR) is defined as less than or equal to 50% of the treated tumor bed is occupied by viable tumor cells. Pathologic non-response is defined as great than 50% of the treated tumor bed is occupied by viable tumor cells.
Measured: Assessed at 10-12 weeks
Secondary outcomes (4)
Objective Response
Objective response is defined as either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters and/or persistence of one or more non-target lesion(s). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Measured: Assessed at baseline, 8 weeks, then every 12 weeks up to 1.4 years
Disease-free Survival
Disease-free survival is defined as the time from date of surgical resection to the date of recurrence or death, whichever occurs first.
Recurrence must be documented by radiologic exams and with biopsy in all cases except for brain metastases (biopsy not required). Abnormal blood studies alone (e.g., elevated transaminases or alkaline phosphatase) are not sufficient evidence of relapse. Whenever possible, histologic proof of recurrence should be obtained unless the lesion is not accessible or a biopsy would cause undue risk to the patient.
Measured: Assessed at baseline, 8 weeks, then every 12 weeks up to 19.4 months
Overall Survival
Overall survival is defined as the time from registration to death or date last known alive, which is the censoring date for patients who are still alive.
Measured: Assessed at every 3 months for 2 years and then every 6 months, up to 2 years 9 months
Associations Between pCR and Best Response
Association between pCR and best response will be reported.
Measured: Assessed at baseline, 8 weeks, then every 12 weeks up to 1.4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2020
- Study start22 Sep 2021
- Primary completion10 Jun 2024
- Study completion31 Jan 2025
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Melanoma of Unknown PrimaryStudies of the same condition, open and under way.
- More trials run by ECOG-ACRIN Cancer Research GroupThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- ECOG-ACRIN Cancer Research Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Leslie A Fecher, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04221438
- Sponsor's protocol ID
- EA6183
- Other IDs
- NCI-2019-07407, EA6183, EA6183, U10CA180820
- Status last verified
- Sep 2026
- First submitted
- 6 Jan 2020
- Last updated
- 6 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Neoadjuvant Study of Encorafenib With Binimetinib in Patients With Resectable Locoregional Metastases From Cutaneous or Unknown Primary Melanoma (Stages III N1B/C/D)
- ClinicalTrials.gov ID
- NCT04221438
- Acronym / sponsor ID
- EA6183
- Conditions
- Melanoma of Unknown Primary, Metastatic Malignant Neoplasm in Lymph Node, Pathologic Stage IIIB Cutaneous Melanoma AJCC v8, Pathologic Stage IIIC Cutaneous Melanoma AJCC v8, Pathologic Stage IIID Cutaneous Melanoma AJCC v8, Recurrent Cutaneous Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- ECOG-ACRIN Cancer Research GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 22 Sep 2021 (actual)
- Primary completion
- 10 Jun 2024 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 9 Jan 2020 (actual)
- Results
- Posted 8 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well encorafenib and binimetinib work before surgery in treating patients with BRAF V600-mutated stage IIIB-D melanoma that has spread to the lymph nodes. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial also studies how well 18F-FLT positron emission tomography (PET)/computed tomography (CT) works in predicting the response of melanoma to encorafenib and binimetinib. 18F-FLT is an imaging agent, sometimes called a tracer. PET and CT are types of imaging scans. Using 18F-FLT PET/CT together with encorafenib and binimetinib may provide more information on melanoma over time.
Detailed description
PRIMARY CLINICAL OBJECTIVE:
- To evaluate the pathologic complete response (pCR) rate of neoadjuvant treatment with encorafenib and binimetinib.
SECONDARY CLINICAL OBJECTIVES:
- To determine response rate (RR) (Response Evaluation Criteria in Solid Tumors [RECIST]), disease-free survival (DFS) and overall survival (OS).
II. To describe correlation of pCR with RR, DFS and OS. III. To assess safety and toxicity.
CORRELATIVE SCIENCE OBJECTIVES:
- To evaluate CD8 positive (+) T cell infiltration and Ki-67 status in tumor or tumor bed pre, during, and post neoadjuvant treatment and the change in CD8+ tumor infiltrating lymphocyte (TIL) with neoadjuvant treatment and correlate with clinical response.
II. To compare local review for pathologic response with central pathology review.
III. To assess the correlation between change in fluorothymidine F-18 (18F-FLT) PET/CT uptake and change in Ki-67.
IMAGING OBJECTIVES:
- To compare the change in 18F-FLT PET/CT uptake (from baseline to post-neoadjuvant therapy) among patients with and without pathologic complete response.
II. To compare post-neoadjuvant 18F-FLT PET/CT uptake among patients with and without pathologic complete response.
III. To estimate an optimal threshold for prediction of pathologic complete response using i) change in 18F-FLT PET/CT uptake, and ii) post-neoadjuvant 18F-FLT PET/CT uptake.
IV. To assess the correlation between change in 18F-FLT PET/CT uptake and change in Ki-67.
OUTLINE:
NEOADJUVANT TREATMENT: Patients receive 18F-FLT intravenously (IV) and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib orally (PO) once daily (QD) and binimetinib PO twice daily (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.
After completion of study treatment, patients are followed up every 3 months for 1 year, then every 6 months for 3 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib | Experimental | Drug: Binimetinib, Procedure: Conventional Surgery, Drug: Encorafenib, Other: Fluorothymidine F-18NEOADJUVANT 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Patient must have histologically proven melanoma that is clinically evident (macroscopic lymphadenectomy [LAD]) stage III B/C/D, (American Joint Committee on Cancer [AJCC] 8th edition) of cutaneous origin or unknown primary. Patients must have at least one clinically evident lymph node metastasis (N1c patients are not eligible).
- Patient must have measurable disease on baseline imaging scans, obtained within 4 weeks prior to registration as defined by RECIST and by the following criteria
- Patient must have BRAF V600 mutation positive based on report from Clinical Laboratory Improvement Act (CLIA) certified laboratory
- Patient must be medically fit to undergo surgery
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (obtained < 14 days prior to registration)
Key exclusion criteria (28 listed)
- Stage IV melanoma
- Patient must not have any prior treatment with BRAF inhibitor (BRAFi) or MEK inhibitor (MEKi)
- Patient must not have any evidence of distant metastases
- Patient must not have any prior adjuvant therapy at this disease presentation; prior immune therapy (such as adjuvant interferon or checkpoint inhibitors) is permitted if >= 6 months from last treatment
- Patient must not have any prior radiation to the site of evaluable disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BinimetinibAlso: NSC 788187, ARRY-438162, MEK162, MektoviGiven PO | Drug | Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib |
| Conventional SurgeryUndergo surgery | Procedure or surgery | Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib |
| EncorafenibAlso: ONO-7702, LGX818Given PO | Drug | Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib |
| Fluorothymidine F-18Also: 18F-FLT, 3'-deoxy-3'- 18F fluorothymidine, FLTGiven IV | Other | Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib |
Primary outcome
Pathologic Complete Response
Time frame: Assessed at 10-12 weeks
Pathologic complete response (pCR) is defined as complete absence of viable tumor in the treated tumor bed. Partial pathologic response (pPR) is defined as less than or equal to 50% of the treated tumor bed is occupied by viable tumor cells. Pathologic non-response is defined as great than 50% of the treated tumor bed is occupied by viable tumor cells.
4 secondary outcomes
Objective Response
Time frame: Assessed at baseline, 8 weeks, then every 12 weeks up to 1.4 years
Disease-free Survival
Time frame: Assessed at baseline, 8 weeks, then every 12 weeks up to 19.4 months
Overall Survival
Time frame: Assessed at every 3 months for 2 years and then every 6 months, up to 2 years 9 months
Associations Between pCR and Best Response
Time frame: Assessed at baseline, 8 weeks, then every 12 weeks up to 1.4 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leslie A Fecher principal investigator
ECOG-ACRIN Cancer Research Group
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Binimetinib, Conventional Surgery and Encorafenib in people with Melanoma of Unknown Primary and Metastatic Malignant Neoplasm in Lymph Node, run by ECOG-ACRIN Cancer Research Group at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic Complete Response (time frame: Assessed at 10-12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.