Advanced or Metastatic Solid Tumors Clinical Trial
— SEACRAFT-1Official 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
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
Status | Recruiting |
Enrollment | 115 |
Est. completion date | November 2025 |
Est. primary completion date | July 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 12 Years to 99 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Australia | Macquarie University | Macquarie Park | New South Wales |
Australia | St. Vincent's Hospital | Melbourne | Victoria |
Australia | Linear Clinical Research, LTD | Perth | |
Canada | London Regional Cancer Center | London | Ontario |
Canada | The Ottawa Hospital | Ottawa | Ontario |
Canada | Princess Margaret Cancer Centre | Toronto | Ontario |
Canada | British Columbia Cancer Agency | Vancouver | British Columbia |
Korea, Republic of | Inje University Haeundae Paik Hospital | Busan | Busan Gwang'yeogsi |
Korea, Republic of | National Cancer Center | Goyang-si | |
Korea, Republic of | Seoul National University Hospital Bundang | Gyeonggi-do | |
Korea, Republic of | Samsung Medical Center | Seoul | Seoul Teugbyeolsi |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Korea, Republic of | The Catholic University Hospital | Seoul | |
United Kingdom | Sarah Cannon Research Institute - HCA Healthcare | City Of London | London |
United Kingdom | Beatson West of Scotland Cancer Center | Glasgow | |
United States | Emory University School of Medicine | Atlanta | Georgia |
United States | University of Alabama | Birmingham | Alabama |
United States | Henry Ford Health System | Detroit | Michigan |
United States | Inova Schar Cancer Institute | Fairfax | Virginia |
United States | NEXT Virginia | Fairfax | Virginia |
United States | The University of Texas MD Anderson Cancer Center | Houston | Texas |
United States | Comprehensive Cancer Center of Nevada (CCCN) | Las Vegas | Nevada |
United States | University of Wisconsin | Madison | Wisconsin |
United States | SCRI Oncology Partners (formerly Tennessee Oncology) | Nashville | Tennessee |
United States | Oregon Health & Science University | Portland | Oregon |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | Florida Cancer Specialists - St. Petersburg | Saint Petersburg | Florida |
United States | University of California, San Francisco | San Francisco | California |
United States | Florida Cancer Specialists - Sarasota | Sarasota | Florida |
Lead Sponsor | Collaborator |
---|---|
Erasca, Inc. |
United States, Australia, Canada, Korea, Republic of, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Duration of Response (DOR) for CNS disease in participants | Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) | Assessed up to 24 months from time of first dose | |
Other | Overall Response Rate (ORR) for CNS disease in participants | Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) | Assessed up to 24 months from time of first dose | |
Other | Disease Control Rate (DCR) for CNS disease in participants | Based on Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) | Assessed up to 24 months from time of first dose | |
Other | Pharmacodynamic assessment | DUSP6: changes from baseline in the expression of DUSP-6 mRNA in blood, a marker of MAPK pathway Inhibition. | Assessed up to 24 months from time of first dose | |
Primary | To evaluate the efficacy of naporafenib administered with trametinib in patients with rat sarcoma viral oncogene (RAS) Q61X solid tumors | Based on assessment of Objective response rate (ORR) per RECIST version 1.1 | Assessed up to 24 months from time of first dose | |
Secondary | Adverse Events | Incidence and severity of treatment-emergent AEs and serious AEs | Assessed up to 24 months from time of first dose | |
Secondary | 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 | |
Secondary | 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 | |
Secondary | Progression Free Survival (PFS) | Based on assessment of radiographic imaging per RECIST version 1.1 | Assessed up to 24 months from time of first dose | |
Secondary | 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 | |
Secondary | Plasma concentration (Cmax) | Maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 | |
Secondary | Time to achieve Cmax (Tmax) | Time to achieve maximum plasma concentration of ERAS-254 and trametinib | Study Day 1 up to Day 29 | |
Secondary | Area under the curve (AUC) | Area under the plasma concentration-time curve | Study Day 1 up to Day 29 | |
Secondary | Overall survival | Survival Status | Assessed up to 24 months from time of first dose |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
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