Perioperative Encobini in BRAFV600 Mutant Stage III (B/C/D) or Oligometastatic Stage IV Melanoma

NCT05097378 | Unknown Phase 2 DMC

• 1 other identifier: PREMIUM
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

A two-arm, randomised trial investigating the response of encorafenib and binimetinib compared to standard adjuvant therapy.

Conditions

Melanoma; Cancer

Outcome Measures

Primary Outcomes (1)

• Pathological response rate

  % of patients with a complete response using Haemotoxylin and Eosin staining of tumour removed at surgery.

  During scheduled surgery

Secondary Outcomes (7)

• Treatment compliance

  Through study completion for an average of 12 months

• Radiological response

  Through study completion for an average of 12 months

• Toxicity of treatment

  Through study completion for an average of 12 months

• Lymphoedema toxicity

  Through study completion for an average of 12 months

• Survival rate

  Through study completion for an average of 12 months

Study Arms (2)

EncoBini Arm

EXPERIMENTAL

Oral encorafenib 450mg once daily and oral binimetinib 45mg twice daily for 8 weeks pre-operative and for up to 44 weeks post-operative.

Drug: Encorafenib + Binimetinib

Standard Arm

ACTIVE COMPARATOR

Immediate surgery followed by Investigator's choice of standard adjuvant therapy to commence within 12 weeks of surgery and to continue for up to 52 weeks.

Drug: Standard Adjuvant Treatment

Interventions

Encorafenib + Binimetinib DRUG

Encorafenib is a potent and highly selective ATP-competitive small molecule RAF kinase inhibitor, which suppresses the RAF/MEK/ERK pathway in tumour cells expressing several mutated forms of BRAF kinase (V600E, D and K). Binimetinib is an ATP-uncompetitive, reversible inhibitor of the kinase activity of mitogen-activated extracellular signal regulated kinase 1 (MEK1) and MEK2. Binimetinib inhibits activation of MEK by BRAF and inhibits MEK kinase activity

Also known as: Braftovi + Mektovi

EncoBini Arm

Standard Adjuvant Treatment DRUG

Standard Adjuvant Treatment

Standard Arm

Eligibility Criteria

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

You may qualify if:

• Written informed consent to participate
• Aged ≥ 18 years old
• AJCC 8th edition stage III (B/C/D), or extracranial oligometastatic stage IV BRAFV600 mutant melanoma, based on histological/cytological and radiological assessments for which surgery is planned, and resection is expected to remove all known tumour(s) with R0 resection margins. 'Oligometastatic stage IV' is defined for the purpose of this trial as M stage disease confined to a single body organ excluding the brain that can be readily removed surgically with anticipated clear margins
• For stage III patients, confirmation of no evidence of distant metastatic disease using preferred imaging modalities including CT body or PET/CT and CT or MRI head
• For stage IV patients, confirmation of no evidence of unresectable metastatic disease, or metastatic disease in more than 1 body organ, using preferred imaging modalities including CT body or PET/CT and CT or MRI head. The site of metastasis should not be in bone, or CNS, or in any other body site where complete resection is not feasible
• The planned resectable disease must be radiologically measurable using standard imaging modalities.
• Baseline tumour assessments must be done within 28 days prior to randomisation
• BRAF V600E or V600K mutation confirmation
• Received no prior BRAF or MEK inhibitors
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Predicted life expectancy \>12 months
• Normal QTc interval (\<480msec) on ECG and left ventricular ejection fraction within normal limits, assessed by echocardiogram or MUGA
• Adequate bone marrow function defined as:
• Absolute neutrophil count (ANC) ≥1.5 x 109 /L
• Haemoglobin (Hb) ≥ 90 g/L

You may not qualify if:

• Prior adjuvant therapy for resected primary or loco-regional melanoma
• Other invasive malignancies diagnosed within the last 2 years which are not in complete remission, or for which additional therapy is required
• Brain or bone metastases
• Non-cutaneous primary site of melanoma
• Prior radiotherapy to the site planned for surgery
• History or current evidence of retinal vein occlusion (RVO) or risk factors for RVO (uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or hypercoagulability syndromes)
• Left ventricular function \<50%
• Significant acute or chronic medical or psychiatric condition, disease or laboratory abnormality which in the judgment of the investigator would place the patient at undue risk or interfere with the trial. Examples include, but are not limited to:
• Patients with uncontrolled ischaemic heart or other cardiovascular event (myocardial infarction (MI), new angina, stroke transient ischaemic attack (TIA), or new congestive cardiac failure (CCF)) within the last 6 months
• Uncontrolled hypertension
• Patients with stable but significant cardiovascular disease defined by heart failure (New York Heart Association Functional Classification (NYHF) III or IV or frequent angina
• Patients with baseline QTC interval \> 480 msec on electrocardiogram (ECG)
• Left ventricular ejection fraction below the lower limit of normal
• Presence of active infection
• Cirrhotic liver disease, known chronic active or acute hepatitis B, or hepatitis C

Sponsors & Collaborators

• CCTU- Cancer Theme: lead
• Pierre Fabre Medicament: collaborator

Study Sites (1)

Addenbrooke's Hospital

Cambridge, England, CB2 2QQ, United Kingdom

Location

MeSH Terms

Conditions

Melanoma; Neoplasms

Interventions

encorafenib; binimetinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Pippa Corrie

  Cambridge University Hospitals NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lisa Bax

CONTACT

+44 (0)1223 348090; lisa.bax@addenbrookes.nhs.uk

Sophie Twelves

CONTACT

sophie.twelves@addenbroookes.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Investigator

Model Details: Neoadjuvant and adjuvant administration schedule

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: October 28, 2021
• Study Start: January 1, 2022
• Primary Completion: September 1, 2023
• Study Completion: January 31, 2024
• Last Updated: October 28, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)