(Neo)Adjuvant BRAF/MEK Inhibition in pN1c Melanoma

NCT05767879 | Unknown Phase 2 DMC

• 2 other identifiers: NL77905.058.212021-002285-40
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma Stage III; In-Transit Metastasis of Cutaneous Melanoma

Keywords

Targeted therapy; In-transit; Melanoma; Neo-adjuvant

Outcome Measures

Primary Outcomes (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.

  8 weeks

Secondary Outcomes (5)

• Evaluate efficacy of treatment related toxicity

  52 weeks

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

  44 weeks

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

  44 weeks

• Efficacy of adjuvant encorafeninb/binimetinib - overall survival

  44 weeks

• Efficacy of adjuvant encorafeninb/binimetinib - treatment related survival

  44 weeks

Study Arms (1)

Neo adjuvant BRAF/MEK inhibition in pN1c Melanoma

EXPERIMENTAL

Neo 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.

Drug: Encorafenib + Binimetinib

Interventions

Encorafenib + Binimetinib DRUG

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.

Neo adjuvant BRAF/MEK inhibition in pN1c Melanoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• Pierre Fabre Laboratories: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2311GP, Netherlands

RECRUITING

MeSH Terms

Conditions

Melanoma

Interventions

encorafenib; binimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

HW Kapiteijn, phd

CONTACT

0715264036; h.w.kapiteijn@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Phd

Study Record Dates

• First Submitted: August 16, 2022
• First Posted: March 14, 2023
• Study Start: January 1, 2022
• Primary Completion: January 1, 2026
• Study Completion: January 1, 2026
• Last Updated: March 14, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)