Trial purpose
Cancer treatment
Tumor type
Skin
Age
18 - 99
Clinical summary
Summary
This study has two stages. In Stage 1, the aim is to select the optimal dose of Naporafenib and Trametinib to be studied in Stage 2.
In Stage 2, the effectiveness of Naporafenib + Trametinib compared to physician's choice of therapy (either dacarbazine chemotherapy, temozolomide chemotherapy or trametinib targeted therapy) will be studied.
Each Stage has multiple arms, and participants will be randomised into arms.
Stage 1 Dose selection Lead in:
- Arm 1 - Naporafenib 100mg orally twice daily + Trametinib 1mg once daily
- Arm 2 - Naporafenib 40mg orally twice daily + Trametinib 0.5mg once daily
- Arm 3- Trametinib 2mg once daily as monotherapy (by itself)
Stage 2
- Arm A - Naporafenib orally twice daily + Trametinib once daily at the dose selected in Stage 1
- Arm B - Physician's choice of either: Dacarbazine chemotherapy intravenous (IV) on Day 1 of each 21-day cycle, OR Temozolomide orally on Day 1 to Day 5 of each 28-day cycle, OR Trametinib monotherapy orally once daily.
Conditions
This trial is treating people with unresectable or metastatic cutaneous (includes acral) melanoma with NRAS mutation who have progressed on or are intolerant to an anti PD1/L1-based regimen
Eligibility
Inclusion
- Willing and able to provide written informed consent
- Age ≥ 18 years
- Histologically or cytologically confirmed unresectable or metastatic cutaneous (includes acral) melanoma.
- 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.
- 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.
- 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.
- ECOG performance status 0, 1 or 2
- Presence of at least 1 measurable lesion according to RECIST v1.1
- Able to swallow oral medication.
Exclusion
- Patients with uveal or mucosal melanoma
- Prior therapy with an ERK-, MEK-, RAF-, or RAS-inhibitor
- 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)
- 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)
- LVEF <50%
- Symptomatic CNS metastases that are neurologically unstable. Patients with controlled CNS metastases are eligible.
- 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.
- Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial
Inclusion
- Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
- Your cancer has not spread to other parts of the body (localised).
- You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
- You are able to swallow medication by mouth.
- You have had a certain type of treatment or surgical procedure.
Exclusion
- You have certain types of non-cancer medical conditions.
- You have had certain treatments, surgical procedures or drugs.
Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.
More information
Trial Identifiers
Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:
Trial sponsor
Erasca, Inc.
Scientific Title
A Randomized, Open-label Phase III Study in Patients With Previously Treated Unresectable or Metastatic NRAS Mutant Cutaneous Melanoma Comparing the Combination of Naporafenib + Trametinib to Physician's Choice of Therapy (Dacarbazine, Temozolomide or Trametinib Monotherapy) With a Dose Optimization lead-in [SEACRAFT-2]
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