Share
Save
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)
Stage 1: To select the optimal dose of naporafenib + trametinib to be studied in Stage 2. Stage 2: To compare progression free survival (PFS) and overall survival (OS) for patients with NRAS-mutant (NRASm) melanoma who are randomized to receive the combination of naporafenib + trametinib to that of patients who are randomized to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy).
Study details:
SEACRAFT-2 is a global, Phase III, open-label, randomized study to assess the efficacy and safety of naporafenib administered with trametinib compared to physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) in patients with unresectable or metastatic NRAS mutant melanoma who have progressed on, or are intolerant to, an anti-programmed death-1 ligand 1 (PD 1/L1)-based regimen. The study will consist of 2 stages: dose optimization in Stage 1 and the Phase 3 portion in Stage 2. A total of approximately 470 eligible patients will be randomized to receive study drug(s) in this study across 2 stages.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2024-04-29
Primary completion: 2028-04-01
Study completion finish: 2028-12-01
Study type
TREATMENT
Phase
PHASE3
Trial ID
NCT06346067
Intervention or treatment
DRUG: Naporafenib
DRUG: Dacarbazine
DRUG: Temozolomide
DRUG: Trametinib
Conditions
- • Advanced or Metastatic NRAS-mutant Melanoma
Find a site
Closest Location:
Calvary Mater Newcastle
Research sites nearby
Select from list below to view details:
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
Hollywood Private Hospital
Nedlands, Western Australia, Australia
Tasman Health Care
Southport, Queensland, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Stage 1 Dose selection Lead-in Arm 1
| DRUG: Naporafenib
|
EXPERIMENTAL: Stage 1 Dose selection Lead-in Arm 2
| DRUG: Naporafenib
|
ACTIVE_COMPARATOR: Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapy
| DRUG: Trametinib
|
EXPERIMENTAL: Stage 2 Arm A
| DRUG: Naporafenib
|
ACTIVE_COMPARATOR: Stage 2 Arm B - Physician's Choice
| DRUG: Dacarbazine
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 6 months from time of first dose |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Objective response rate (ORR) based on assessment of radiographic imaging RECIST v1.1 | Assessed up to 6 months from time of first dose |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Time to achieve maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 |
Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 | Area under the plasma concentration-time curve | Study Day 1 up to Day 29 |
Stage 2: To compare PFS and OS for patients who are randomized to receive the combination of naporafenib + trametinib to that of patients who receive physician's choice of therapy (dacarbazine, temozolomide, or trametinib monotherapy) | * Progression free survival (PFS) based on assessment of radiographic imaging per RECIST v1.1 * Survival status | Assessed up to 24 months from time of first dose |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Adverse Events | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 24 months from time of first dose |
Duration of Response (DOR) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose] |
Time to Response (TTR) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose] |
Disease Control Rate (DCR) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose] |
Overall Response Rate (ORR) | Based on the assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose |
Plasma concentration (Cmax):Stage 1 only | Maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 |
Area under the curve (AUC):Stage 1 only | Area under the plasma concentration-time curve | Study Day 1 up to Day 29 |
Quality of Life: To assess disease and treatment-related QOL in patients with NRASm melanoma. | Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire \[QLQ\]-C30 subscales and PRO CTCAE® symptom items specific to the potential cutaneous toxicities. | Assessed up to 24 months from time of first dose |
Frequently Asked Questions
Please note: some questions and answers are submitted by anonymous patients or using AI, and have not been verified by Clinrol
No questions submitted. Be the first to ask a question!