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Melanoma Stage IIIPhase 2NCT05767879

(Neo)Adjuvant BRAF/MEK Inhibition in pN1c Melanoma

A Phase 2 study testing Encorafenib + Binimetinib in people with Melanoma Stage III and In-Transit Metastasis of Cutaneous Melanoma, run by Leiden University Medical Center at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Phase 2 open-label single arm intervention study administering encorafenib/binimetinib in neo-adjuvant setting followed by surgery and subsequent adjuvant encorafenib/binimetinib in in-transit melanoma patients without lymph node and distant metastases. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Encorafenib + Binimetinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
28 participants
Where
1 siteNetherlands
Study dates
1 Jan 2022to 1 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

  • Age over 18 years old
  • World Health Organization (WHO) Performance Status 0 or I
  • Primary cutaneous melanoma or unknown primary melanoma with pathologically confirmed in-transit metastatic melanoma
  • Patients must have undergone complete disease staging including: PET-CT scan and MRI scan
  • Patients must be medically fit to undergo surgery
  • Patients must be able to take oral medication
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  • No prior anticancer systemic treatment (including chemotherapy, immunotherapy, oncolytic viral therapy, other systemic therapies)
  • No prior radiotherapy to site of interest (surgical therapy is allowed; in order to obtain pathological information of the melanoma)
  • Screening laboratory values must meet the following criteria: WBC ≥ 2.0x109/L, Neutrophils ≥ 1.0x109/L, Platelets ≥ 100 x109/L, Hemoglobin ≥ 6.5 mmol/L, AST ≤ 2.5 x ULN, ALT ≤ 2.5 x ULN, Total bilirubin ≤ 1.5 X ULN, INR and PTT in normal range, LDH < 2xULN. Serum creatinine ≤ 1.5 × ULN; or calculated creatinine clearance ≥ 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m2.
  • Absence of additional severe and/or uncontrolled concurrent disease

Who cannot join

  • Presence of regional lymph node metastases
  • Presence of distant metastases
  • Current treatment with antiretroviral drugs, herbal remedies and drugs that are strong inhibitors or inducers of CYP3A and CYP2C8
  • Patients with active bacterial infections with systemic manifestations (malaise, fever, leukocytosis) are not eligible until completion of appropriate therapy
  • Underlying medical conditions that, in the Investigator's opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events
  • History of congestive heart failure, active cardiac conditions, including unstable coronary syndromes (unstable or severe angina, recent myocardial infarction), significant arrhythmias and severe valvular disease must be evaluated for risks of undergoing general anesthesia. Furthermore, enlarged QTc interval, uncontrolled hypertension, poor left ventricular function (< 50%, as determined by MUGA scan) and recent thromboembolic or cerebral event.
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  • History of central serous retinopathy or retinal vein occlusion
  • Active intestinal disease interfering with oral drug absorption
  • Patients who are unable to be temporally removed from chronic anti-coagulation therapy for operation
  • (Neo)Adjuvant BRAF/MEKi for pN1c melanoma, version 5, 31 October 2021
  • Other malignancy within 2 years prior to entry into the study, except for treated non-melanoma skin cancer and in situ cervical carcinoma
  • 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 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
  • Pregnancy or nursing

Trial locations and contacts

1 site in 1 country.

HW Kapiteijn, phd contact

0715264036

h.w.kapiteijn@lumc.nl

Netherlands1 site, 1 recruiting

  • Leiden University Medical Center

    Leiden, South Holland, 2311GP

    Ellen Kapiteijn, phd, (071) 526 4036, h.w.kapiteijn@lumc.nl

    Daan Rauwerdink, drs, d.j.w.rauwerdink@lumc.nl

    Recruiting

Other trials in Netherlands

About this study

Official title: Open Label Phase 2 Study Neo-Adjuvant BRAF/MEK Inhibition Followed by Surgery and Adjuvant BRAF/MEK Inhibition in In-transit Melanoma Metastases (NASAM)

Phase 2 open-label single arm intervention study administering encorafenib/binimetinib in neo-adjuvant setting followed by surgery and subsequent adjuvant encorafenib/binimetinib in in-transit melanoma patients without lymph node and distant metastases.

Read the detailed description

Phase 2 open-label single arm intervention study administering encorafenib/binimetinib in neo-adjuvant setting followed by surgery and subsequent adjuvant encorafenib/binimetinib in patients diagnosed solely with in-transit metastatic melanoma.

Primary objective is to determine the efficacy of neo-adjuvant encorafenib/binimetinib as measured by pathological response rate (partial-, complete- and no response). In the biopsy at week 0 the viability will be judged and will be graded according to the amount of tumor necrosis: >50% tumor necrosis with <50% viable tumor cells, <50% necrosis with >50% viable tumor cells and 100% necrosis without viable tumor cells. Partial response is defined as a decrease of at least 50% of the viable tumor cells and complete response as 100% decrease of tumor cells, whereas no response is defined as more than 50% of viable tumor cells present.

Secondary objectives are to assess efficacy of adjuvant BRAF/MEK inhibition, measured as local recurrence free survival (LRFS), distant metastases-free survival (DFMS), recurrence free survival (local and/or distant recurrence, RFS) and overall survival (OS). Additionally, the toxicity of the administered regimen will be assessed by analyzing the frequency- and type of adverse events, and occurrences of therapy interruption, dose reduction and or therapy cessation. Moreover, an exploration of drug measurements and ctDNA in blood and additional research of biopsies / resections will be done.

Being tested
Encorafenib + Binimetinib
Keywords
Targeted therapy, In-transit, Melanoma, Neo-adjuvant
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Encorafenib + BinimetinibDrug

    In the open label phase II study, the combination of BRAF/MEK inhibition with encorafenib/binimetinib in the neo-adjuvant setting will be investigated.

    Furthermore, efficacy of adjuvant BRAF/MEK inhibition with encorafenib/binimetinib, for 44 weeks will be evaluated.

Study groups in NCT05767879
Study groupRoleWhat they receive
Neo adjuvant BRAF/MEK inhibition in pN1c MelanomaExperimentalNeo adjuvant BRAF/MEK inhibition (encorafenib/binimetinib). Patients receive encorafenib 450 mg once daily for a period of 8 weeks. Patients receive 45 mg binimetinib twice daily for a period of 8 weeks. After the neo-adjuvant therapie, patients will receive encorafenib 450 mg once daily fand binimetinib 45mg twice daily for 44 weeks.
Receives: Drug: Encorafenib + Binimetinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Efficacy of neo-adjuvant encorafenib/binimetinib

    Primary outcome is to determine the efficacy of neo-adjuvant eEncorafenib/bBinimetinib as measured by pathological response rate (partial-, complete- and no response). In the biopsy at week 0 the viability will be judged and will be graded according to the amount of tumor necrosis: >50% tumor necrosis with <50% viable tumor cells, <50% necrosis with >50% viable tumor cells and 100% necrosis without viable tumor cells. Partial response is defined as a decrease of at least 50% of the viable tumor cells, and complete response is defined as more than 90% a decrease of more than 90% of the tumor cells, whereas no response is defined as more than 50% of viable tumor cells present.

    Measured: 8 weeks

Secondary outcomes (5)

  1. Evaluate efficacy of treatment related toxicity

    analyzing the frequency- and type of adverse events, and occurrences of therapy interruption, dose reduction and or therapycessation. Adverse events severity will be graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 5.0. Adverse events associated with BRAF/MEK inhibition will be termed as treatment related or potentially treatment related, adverse events which are not known class effects of BRAF/MEK inhibitors will be described as adverse events not treatment related. Adverse event assessment will take place from therapy initiation up to completion of adjuvant treatment (week 44) and 30 das after.

    Measured: 52 weeks

  2. Efficacy of adjuvant encorafenib/binimetinib - local recurrece free survival (LRFS)

    To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment.

    Local disease recurrence is defined as pathologically confirmed metastasic melanoma in scar tissue and or recurrence of melanoma within 2cm of the surgical scar of primary melanoma of the previously removed melanoma.

    Local disease recurrence will be measured from start of adjuvant therapy up to disease recurrence confirmation.

    Measured: 44 weeks

  3. Efficacy of adjuvant encorafeninb/binimetinib - distant metastases-free survival (DFMS)

    To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment.

    Distant metastases free survival (DFMS) is defined as the moment of pathologically and or radiologically disease confirmation.

    Distant metastatic disease includes, distant lymph nodes and organs. Distant metastatic free survival will be calculated using the start of therapy up to the moment of distant metastatic disease confirmation or last follow-up moment.

    Measured: 44 weeks

  4. Efficacy of adjuvant encorafeninb/binimetinib - overall survival

    To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment.

    Overall survival is defined as the moment of primary melanoma up to decease.

    Measured: 44 weeks

  5. Efficacy of adjuvant encorafeninb/binimetinib - treatment related survival

    To assess efficacy of adjuvant BRAF/MEK inhibition by analyzing the surgical site clinically (bimonthly) and radiologically (every 4 months) during the adjuvant treatment.

    The moment of start of adjuvant therapy up to decease or last follow-up moment.

    Measured: 44 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2023
  2. Study start1 Jan 2022
  3. Primary completion1 Jan 2026 (estimated)
  4. Study completion1 Jan 2026 (estimated)

Resources

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
28 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05767879
Sponsor's protocol ID
NL77905.058.21
Other IDs
2021-002285-40
Status last verified
Mar 2023
First submitted
16 Aug 2022
Last updated
14 Mar 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Encorafenib + Binimetinib in people with Melanoma Stage III and In-Transit Metastasis of Cutaneous Melanoma, run by Leiden University Medical Center at 1 site in Netherlands.

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 10 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 14 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. 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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact HW Kapiteijn, phd (0715264036, h.w.kapiteijn@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Efficacy of neo-adjuvant encorafenib/binimetinib (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05767879.

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 14 Mar 2023.

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