Trial Title:
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations
NCT ID:
NCT05907304
Condition:
Advanced or Metastatic Solid Tumors
Conditions: Official terms:
Trametinib
Naporafenib
Conditions: Keywords:
Melanoma
Non-small cell lung cancer
Thyroid cancer
Colorectal Cancer (cohort full)
Pancreatic Cancer
Other solid tumors harboring a RAS Q61X mutation
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Naporafenib
Description:
Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor
Arm group label:
Naporafenib + Trametinib
Other name:
LXH254
Other name:
ERAS-254
Intervention type:
Drug
Intervention name:
Trametinib
Description:
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Arm group label:
Naporafenib + Trametinib
Other name:
Mekinist
Summary:
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat
sarcoma viral oncogene (RAS) Q61X solid tumors
- To evaluate the safety and tolerability of naporafenib administered with trametinib
in patients with RAS Q61X solid tumors
- To characterize the pharmacokinetic (PK) profile of naporafenib and trametinib when
administered to patients with RAS Q61X solid tumors
Detailed description:
SEACRAFT-1 is an open-label study to assess the safety and efficacy of naporafenib
administered with trametinib in previously treated patients with locally advanced
unresectable or metastatic RAS Q61X solid tumor malignancies. The study will enroll a
total of approximately 100 adult patients; a sub-study will enroll approximately 15
adolescent patients ≥12 and <18 years for a total sample size of approximately 115.
Patients with a locally advanced unresectable or metastatic solid tumor malignancy that
is not responsive to standard therapies or for which there is no standard therapy are
eligible. Patients with primary central nervous system (CNS) tumors are not eligible.
Documentation of a RAS Q61X mutation in tumor tissue prior to the first dose of study
treatment is required.
Criteria for eligibility:
Criteria:
Key Inclusion Criteria:
1. Willing and able to provide written informed consent
2. Age ≥ 12 years
3. A locally advanced or metastatic tumor who has progressed on or for which no
standard therapy exists. Patients who are intolerant to standard therapy or who are
not a candidate for standard therapy (in the opinion of the Investigator) or who
decline standard therapy are also eligible.
4. Documentation of a RAS Q61X mutation (tumor tissue or blood) prior to first dose of
study treatment 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. ECOG performance status 0, 1 or 2
7. Presence of at least 1 measurable lesion according to RECIST v1.1
8. Able to swallow oral medication.
Exclusion Criteria:
1. Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
2. Impairment of GI function or gastrointestinal (GI) disease that may significantly
alter the absorption of study treatment (e.g., ulcerative diseases, uncontrolled
nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
3. 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)
4. Corrected QT interval using Fridericia's formula (QTcF) at Screening >450 ms based
on triplicate average NOTE: criterion does not apply to patients with a right or
left bundle branch block
5. LVEF <50%
6. All primary CNS tumors
7. Symptomatic CNS metastases that are neurologically unstable. Patients with
controlled CNS metastases are eligible.
8. Patients receiving treatment with medications that are known to be strong inhibitors
and/or inducers of cytochrome P450 (CYP)3A; substrates of CYP2C8, CYP2C9, and CYP3A
with a narrow therapeutic index and sensitive substrates of CYP3A;
9. Are pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the trial
Gender:
All
Minimum age:
12 Years
Maximum age:
99 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Alabama
Address:
City:
Birmingham
Zip:
35294
Country:
United States
Status:
Withdrawn
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Facility:
Name:
Yale Cancer Center
Address:
City:
New Haven
Zip:
06510
Country:
United States
Status:
Recruiting
Facility:
Name:
Florida Cancer Specialists - St. Petersburg
Address:
City:
Saint Petersburg
Zip:
33705
Country:
United States
Status:
Recruiting
Facility:
Name:
Florida Cancer Specialists - Sarasota
Address:
City:
Sarasota
Zip:
34232
Country:
United States
Status:
Recruiting
Facility:
Name:
Emory University School of Medicine
Address:
City:
Atlanta
Zip:
30322
Country:
United States
Status:
Recruiting
Facility:
Name:
Henry Ford Health System
Address:
City:
Detroit
Zip:
48202
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:
Comprehensive Cancer Center of Nevada (CCCN)
Address:
City:
Las Vegas
Zip:
89169
Country:
United States
Status:
Recruiting
Facility:
Name:
Oregon Health & Science University
Address:
City:
Portland
Zip:
97239
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:
The University of Texas MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Facility:
Name:
Inova Schar Cancer Institute
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
NEXT Virginia
Address:
City:
Fairfax
Zip:
22031
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Wisconsin
Address:
City:
Madison
Zip:
53792
Country:
United States
Status:
Recruiting
Facility:
Name:
Macquarie University
Address:
City:
Macquarie Park
Country:
Australia
Status:
Recruiting
Facility:
Name:
St. Vincent's Hospital
Address:
City:
Melbourne
Country:
Australia
Status:
Recruiting
Facility:
Name:
Linear Clinical Research, LTD
Address:
City:
Perth
Country:
Australia
Status:
Recruiting
Facility:
Name:
Cross Cancer Institute- Alberta Health Services (AHS)
Address:
City:
Edmonton
Zip:
T6G 1Z2
Country:
Canada
Status:
Recruiting
Facility:
Name:
British Columbia Cancer Agency
Address:
City:
Vancouver
Zip:
V5Z 4E6
Country:
Canada
Status:
Recruiting
Facility:
Name:
London Regional Cancer Center
Address:
City:
London
Country:
Canada
Status:
Recruiting
Facility:
Name:
The Ottawa Hospital
Address:
City:
Ottawa
Country:
Canada
Status:
Withdrawn
Facility:
Name:
Princess Margaret Cancer Centre
Address:
City:
Toronto
Zip:
M5G 2M9
Country:
Canada
Status:
Recruiting
Facility:
Name:
Inje University Haeundae Paik Hospital
Address:
City:
Busan
Zip:
48108
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Zip:
06351
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
National Cancer Center
Address:
City:
Goyang-si
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Seoul National University Hospital Bundang
Address:
City:
Gyeonggi-do
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
The Catholic University Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Facility:
Name:
Sarah Cannon Research Institute - HCA Healthcare
Address:
City:
City Of London
Zip:
W1G 6AD
Country:
United Kingdom
Status:
Recruiting
Facility:
Name:
Beatson West of Scotland Cancer Center
Address:
City:
Glasgow
Country:
United Kingdom
Status:
Recruiting
Start date:
August 17, 2023
Completion date:
November 2025
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/NCT05907304
