Trial Title:
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)
NCT ID:
NCT06346067
Condition:
Advanced or Metastatic NRAS-mutant Melanoma
Conditions: Official terms:
Melanoma
Temozolomide
Dacarbazine
Trametinib
Naporafenib
Conditions: Keywords:
Melanoma
NRAS Mutant
Cutaneous Melanoma
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Naporafenib
Description:
Naporafenib (ERAS-254) is an experimental Pan-Raf inhibitor
Arm group label:
Stage 1 Dose selection Lead-in Arm 1
Arm group label:
Stage 1 Dose selection Lead-in Arm 2
Arm group label:
Stage 2 Arm A
Other name:
ERAS-254
Other name:
LXH254
Intervention type:
Drug
Intervention name:
Dacarbazine
Description:
Dacarbazine IV - Day 1
Arm group label:
Stage 2 Arm B - Physician's Choice
Other name:
DTIC
Intervention type:
Drug
Intervention name:
Temozolomide
Description:
Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle
Arm group label:
Stage 2 Arm B - Physician's Choice
Other name:
Temodar
Other name:
TMZ
Intervention type:
Drug
Intervention name:
Trametinib
Description:
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Arm group label:
Stage 1 Dose selection Lead-in Arm 1
Arm group label:
Stage 1 Dose selection Lead-in Arm 2
Arm group label:
Stage 1 Dose selection Lead-in Arm 3 Trametinib monotherapy
Arm group label:
Stage 2 Arm A
Arm group label:
Stage 2 Arm B - Physician's Choice
Other name:
Mekinist
Summary:
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).
Detailed description:
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.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
1. Willing and able to provide written informed consent
2. Age ≥ 18 years
3. Histologically or cytologically confirmed unresectable or metastatic cutaneous
(includes acral) melanoma.
4. Documentation of an NRAS mutation (tumor tissue or blood) prior to first dose of
study drug(s) as determined locally with an analytically validated assay in a
certified testing laboratory.
5. Archival tumor tissue collected within 5 years prior to enrollment must be confirmed
to be available at the time of Screening, which may be submitted before or after
enrollment for exploratory biomarker analysis.
6. Must have received an anti-PD-1/L1 based regimen (monotherapy or combination).
Patient must have documented disease progression either while receiving therapy or
within 12 weeks of last dose of the most recent anti-PD-1/L1 based regimen; the
patient is eligible if they have received other therapies between the most recent
anti-PD-1/L1 based regimen and enrollment.
7. ECOG performance status 0, 1 or 2
8. Presence of at least 1 measurable lesion according to RECIST v1.1
9. Able to swallow oral medication.
Key Exclusion Criteria:
1. Patients with uveal or mucosal melanoma
2. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
3. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of study drug(s) (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
4. 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 or hypercoagulability syndrome)
5. LVEF <50%
6. Symptomatic CNS metastases that are neurologically unstable. Patients with
controlled CNS metastases are eligible.
7. Patients receiving treatment with herbal medicine known to cause liver toxicity,
which cannot be discontinued 7 days prior to first dose of study drug(s) and for the
duration of the study.
8. Are pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial
Gender:
All
Minimum age:
18 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Facility:
Name:
The Melanoma and Skin Care Institute
Address:
City:
Englewood
Zip:
80113
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Miami Sylvester Cancer
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Facility:
Name:
Barbara Ann Karmanos Cancer Institute
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Facility:
Name:
Washington University School of Medicine
Address:
City:
Saint Louis
Zip:
63110
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Sloan Kettering Cancer Center
Address:
City:
New York
Zip:
10065
Country:
United States
Status:
Recruiting
Facility:
Name:
Cleveland Clinic Foundation
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Facility:
Name:
SCRI Oncology Partners (formerly Tennessee Oncology)
Address:
City:
Nashville
Zip:
37203
Country:
United States
Status:
Recruiting
Facility:
Name:
Texas Oncology- Austin Midtown
Address:
City:
Austin
Zip:
78705
Country:
United States
Status:
Recruiting
Facility:
Name:
Texas Oncology - Baylor Charles A. Sammons Cancer Center
Address:
City:
Dallas
Zip:
75246
Country:
United States
Status:
Recruiting
Facility:
Name:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
Virginia Oncology Associates
Address:
City:
Norfolk
Zip:
23502-1871
Country:
United States
Status:
Recruiting
Facility:
Name:
Fred Hutchinson Cancer Center
Address:
City:
Seattle
Zip:
98109
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Wisconsin
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Facility:
Name:
Calvary Mater Newcastle
Address:
City:
Waratah
Zip:
2298
Country:
Australia
Status:
Recruiting
Facility:
Name:
Tasman Health Care
Address:
City:
Southport
Zip:
4215
Country:
Australia
Status:
Recruiting
Facility:
Name:
Princess Alexandra Hospital
Address:
City:
Woolloongabba
Zip:
4102
Country:
Australia
Status:
Recruiting
Facility:
Name:
Peter MacCallum Cancer Institute
Address:
City:
Melbourne
Zip:
3000
Country:
Australia
Status:
Recruiting
Facility:
Name:
Hollywood Private Hospital
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Facility:
Name:
Alfred Hospital
Address:
City:
Melbourne
Zip:
3004
Country:
Australia
Status:
Recruiting
Facility:
Name:
Fakultni nemocnice Hradec Kralove
Address:
City:
Nový Hradec Králové
Zip:
50005
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Sanatorium Profesora Arenbergera
Address:
City:
Prague
Zip:
1502
Country:
Czechia
Status:
Recruiting
Facility:
Name:
Centre Hospitalier du Mans
Address:
City:
Le Mans
Zip:
72000
Country:
France
Status:
Recruiting
Facility:
Name:
Centre Hospitalier Lyon-Sud
Address:
City:
Lyon
Zip:
69310
Country:
France
Status:
Recruiting
Facility:
Name:
Hospital Ambroise Pairs
Address:
City:
Paris
Zip:
75010
Country:
France
Status:
Recruiting
Facility:
Name:
APHP - Hopital Saint Louis
Address:
City:
Paris
Zip:
9001
Country:
France
Status:
Recruiting
Facility:
Name:
Radboud University
Address:
City:
Nijmegen
Zip:
6525 GA
Country:
Netherlands
Status:
Recruiting
Facility:
Name:
Hospital General Universitario Gregorio Marañón
Address:
City:
Madrid
Zip:
28007
Country:
Spain
Status:
Recruiting
Facility:
Name:
Hospital Universitario Ramon y Cajal
Address:
City:
Madrid
Zip:
28034
Country:
Spain
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute - HCA Healthcare
Address:
City:
City of London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Start date:
April 29, 2024
Completion date:
December 2028
Lead sponsor:
Agency:
Erasca, Inc.
Agency class:
Industry
Source:
Erasca, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06346067
