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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05907304




Registration number
NCT05907304
Ethics application status
Date submitted
30/05/2023
Date registered
18/06/2023
Date last updated
26/07/2024

Titles & IDs
Public title
A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations
Scientific title
An Open-label Study to Assess the Safety and Efficacy of Naporafenib (ERAS-254) Administered With Trametinib in Previously Treated Patients With Locally Advanced Unresectable or Metastatic Solid Tumor Malignancies With RAS Q61X Mutations
Secondary ID [1] 0 0
ERAS-254-01
Universal Trial Number (UTN)
Trial acronym
SEACRAFT-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced or Metastatic Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Naporafenib
Treatment: Drugs - Trametinib

Experimental: Naporafenib + Trametinib - Naporafenib (ERAS-254) 200 mg twice daily (BID) Trametinib 1 mg once daily (QD)


Treatment: Drugs: Naporafenib
Naporafenib (ERAS-254) 200 mg twice daily (BID) of an experimental Pan-Raf inhibitor

Treatment: Drugs: Trametinib
Trametinib is an FDA approved anticancer medication that targets MEK1 and MEK2.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors
Timepoint [1] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [1] 0 0
Adverse Events
Timepoint [1] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [2] 0 0
Duration of Response (DOR)
Timepoint [2] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [3] 0 0
Time to Response (TTR)
Timepoint [3] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Timepoint [5] 0 0
Assessed up to 24 months from time of first dose
Secondary outcome [6] 0 0
Plasma concentration (Cmax)
Timepoint [6] 0 0
Study Day 1 up to Day 29
Secondary outcome [7] 0 0
Time to achieve Cmax (Tmax)
Timepoint [7] 0 0
Study Day 1 up to Day 29
Secondary outcome [8] 0 0
Area under the curve (AUC)
Timepoint [8] 0 0
Study Day 1 up to Day 29
Secondary outcome [9] 0 0
Overall survival
Timepoint [9] 0 0
Assessed up to 24 months from time of first dose

Eligibility
Key inclusion criteria
Key

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.
Minimum age
12 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/11/2025
Actual
Sample size
Target
115
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Macquarie University - Macquarie Park
Recruitment hospital [2] 0 0
St. Vincent's Hospital - Melbourne
Recruitment hospital [3] 0 0
Linear Clinical Research, LTD - Perth
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment postcode(s) [2] 0 0
- Melbourne
Recruitment postcode(s) [3] 0 0
- Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
Nevada
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
United States of America
State/province [13] 0 0
Wisconsin
Country [14] 0 0
Canada
State/province [14] 0 0
Alberta
Country [15] 0 0
Canada
State/province [15] 0 0
British Columbia
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Korea, Republic of
State/province [17] 0 0
Busan Gwang'yeogsi
Country [18] 0 0
Korea, Republic of
State/province [18] 0 0
Seoul Teugbyeolsi
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Goyang-si
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Gyeonggi-do
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
United Kingdom
State/province [22] 0 0
London
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Glasgow

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Erasca, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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
Trial website
https://clinicaltrials.gov/study/NCT05907304
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Joyce Antal, MS
Address 0 0
Clinical Development
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Erasca Clinical Team
Address 0 0
Country 0 0
Phone 0 0
1-858-465-6511
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05907304