Active, not recruiting
Phase 3
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2)
Condition(s) studied
Advanced or Metastatic NRAS-mutant Melanoma
Investigational drug(s) / intervention(s)
NaporafenibDacarbazineTemozolomideTrametinib
Naporafenib: Naporafenib (ERAS-254) is an experimental Pan-Raf inhibitor
Dacarbazine: Dacarbazine IV - Day 1
Temozolomide: Temozolomide 200 mg/m2/day PO on Day 1 to Day 5 of each 28-day cycle
Trametinib: Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Study 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).
Eligibility
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
Primary outcome measure(s)
- Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 — Assessed up to 6 months from time of first dose
Incidence and severity of treatment-emergent AEs and serious AEs
- Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 — Assessed up to 6 months from time of first dose
Objective response rate (ORR) based on assessment of radiographic imaging RECIST v1.1
- Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 — Study Day 1 up to Day 29
Maximum plasma concentration of ERAS-254 and trametinib
- Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 — Study Day 1 up to Day 29
Time to achieve maximum plasma concentration of ERAS-254 and trametinib
- Stage 1:To select the optimal dose of naporafenib + trametinib to be studied in Stage 2 — Study Day 1 up to Day 29
Area under the plasma concentration-time curve
- 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) — Assessed up to 24 months from time of first dose
* Progression free survival (PFS) based on assessment of radiographic imaging per RECIST v1.1
* Survival status
Trial sites (59)
| Facility | City | Region | Status |
|---|
| Mayo Clinic - Arizona |
Phoenix |
Arizona |
|
| University of California, San Francisco |
San Francisco |
California |
|
| The Melanoma and Skin Care Institute |
Englewood |
Colorado |
|
| Mayo Clinic - Florida |
Jacksonville |
Florida |
|
| University of Miami Sylvester Cancer |
Miami |
Florida |
|
| University of Kansas Cancer Center |
Kansas City |
Kansas |
|
| Ochsner Clinic Foundation |
Jefferson |
Louisiana |
|
| Massachusetts General Hospital |
Boston |
Massachusetts |
|
| Barbara Ann Karmanos Cancer Institute |
Detroit |
Michigan |
|
| Mayo Clinic |
Rochester |
Minnesota |
|
| Washington University School of Medicine |
St Louis |
Missouri |
|
| Memorial Sloan Kettering Cancer Center |
New York |
New York |
|
| Cleveland Clinic Foundation |
Cleveland |
Ohio |
|
| SCRI Oncology Partners (formerly Tennessee Oncology) |
Nashville |
Tennessee |
|
| Texas Oncology- Austin Midtown |
Austin |
Texas |
|
| Texas Oncology - Baylor Charles A. Sammons Cancer Center |
Dallas |
Texas |
|
| The University of Texas MD Anderson Cancer Center |
Houston |
Texas |
|
| The University of Utah - Huntsman Cancer Institute (HCI) |
Salt Lake City |
Utah |
|
| Virginia Oncology Associates |
Norfolk |
Virginia |
|
| Fred Hutchinson Cancer Center |
Seattle |
Washington |
|
| University of Wisconsin |
Madison |
Wisconsin |
|
| Calvary Mater Newcastle |
Waratah |
New South Wales |
|
| Tasman Health Care |
Southport |
Queensland |
|
| Princess Alexandra Hospital |
Woolloongabba |
Queensland |
|
| Peter MacCallum Cancer Institute |
Melbourne |
Victoria |
|
| Hollywood Private Hospital |
Nedlands |
Western Australia |
|
| Alfred Hospital |
Melbourne |
Australia |
|
| Queen Elizabeth II Health Sciences Centre |
Halifax |
Nova Scotia |
|
| McGill University Health Centre |
Montreal |
Quebec |
|
| Masarykuv Onkologicky Ustav-MOU |
Brno |
Czechia |
|
| Fakultni nemocnice Hradec Kralove |
Nový Hradec Králové |
Czechia |
|
| Sanatorium Profesora Arenbergera |
Prague |
Czechia |
|
| Centre Hospitalier Universitaire (CHU) de Bordeaux - Hospitalier Saint-Andre |
Bordeaux |
France |
|
| CHU Dijon Bourgogne - Hopital Francois Mitterand (Hopital du Bocage) |
Dijon |
France |
|
| Centre Hospitalier du Mans |
Le Mans |
France |
|
| CHRU de Lille - Hôpital Claude Huriez |
Lille |
France |
|
| Centre Hospitalier Lyon-Sud |
Lyon |
France |
|
| Assistance Publique Hopitaux de Marseille (AP-HM) - Hopital de la Timone |
Marseille |
France |
|
| Hospital Ambroise Pairs |
Paris |
France |
|
| APHP - Hopital Saint Louis |
Paris |
France |
|
+ 19 more sites — see the full list on the official registry below.
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