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Kinase Inhibitor

Phase Ib, Defactinib, Avutometinib, and Encorafenib (Cohort B) for Melanoma (DETERMINE Trial)

Phase 1 & 2

Recruiting

Led By Howard Colman, MD, PhD

Research Sponsored by University of Utah

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Must have a tumor with known RAS, BRAF, and NF1 mutation status using a validated testing method prior to enrollment

Must have at least 1 untreated parenchymal brain metastasis with minimal dimension of ≥ 0.5 cm diameter and maximal dimension ≤ 4 cm diameter, measured from a gadolinium enhanced MRI T1 sequence. Note: Subject may have received prior resection or radiation therapy for prior brain metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

DETERMINE Trial Summary

This trial is testing a combination of drugs (defactinib, avutometinib, and encorafenib) in patients with advanced melanoma that has spread to the brain. The

Who is the study for?

This trial is for advanced melanoma patients with brain metastases who didn't respond to immune checkpoint inhibitors. It's specifically for those with certain genetic mutations (RAS, BRAF V600E/K, NF1) or without these mutations (triple wild type). Patients must have at least one untreated brain metastasis to qualify.Check my eligibility

What is being tested?

The study tests defactinib and avutometinib's effectiveness on various melanoma genetic types in the brain. For BRAF V600E/K mutants, it also adds encorafenib. The goal is to see how well these drugs work alone or combined and assess their safety.See study design

What are the potential side effects?

While specific side effects aren't listed here, common ones may include fatigue, nausea, skin reactions from targeted therapies like rash or dryness, liver function changes, and potential bleeding or swelling in the brain from tumor treatment.

DETERMINE Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My tumor's RAS, BRAF, and NF1 mutation status is known.

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I have at least one brain tumor that hasn't been treated, measuring between 0.5 and 4 cm.

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I am fully active or able to carry out light work.

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My skin cancer has spread to my brain.

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I have had at least one immunotherapy treatment before.

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I am 18 years old or older.

DETERMINE Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Frequency of dose limiting toxicities (DLTs).The frequency of adverse events (AEs) and serious adverse events (SAEs) characterized by type, severity (as defined by the NIH CTCAE, version 5.0), seriousness, duration, and relationship to study treatment.

Response rate defined as Partial Response (PR) + Complete Response (CR) using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria of all measurable target lesions present at the time of enrollment on trial.

Secondary outcome measures

Disease control rate as defined by the proportion of subjects achieving a confirmed PR, CR, and SD as defined by Neuro-Oncology Brain Metastases (RANO-BM) criteria.

Duration of response (DoR)

Progression-free survival (PFS) as defined as the time from study drug initiation to the time documented disease progression (as assessed by Neuro-Oncology Brain Metastases (RANO-BM) criteria) or death from any cause.

+2 more

DETERMINE Trial Design

3Treatment groups

Experimental Treatment

Group I: Phase Ib, Defactinib, Avutometinib, and Encorafenib (Cohort B)Experimental Treatment3 Interventions

Avutometinib will be administered at 3.2 mg biweekly orally (e.g., Monday/Thursday, Tuesday/Friday, or Wednesday/Saturday) for 3 weeks, followed by a 1-week rest period, in each 4-week (28-day) cycle. Defactinib will be administered at 200 mg twice a day orally for 3 weeks, followed by a 1-week rest period, in each 4-week (28-day) cycle. Encorafenib will be administered orally to a small cohort to a limited dose escalation cohort using a Bayesian optimal interval (BOIN) design to evaluate safety, toxicity, and recommended phase II dose for dosage of encorafenib when combined with avutometinib and defactinib. Dose escalation levels for Encorafenib: Dose Level -1: 225 mg Daily (three 75mg capsules) Dose Level 0: 300 mg Daily (four 75mg capsules) Dose Level 1: 450 mg Daily (six 75mg capsules)

Group II: Phase II, Defactinib, Avutometinib, and Encorafenib (Cohort B)Experimental Treatment3 Interventions

Group III: Phase II, Defactinib and Avutometinib (Cohort A)Experimental Treatment2 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Encorafenib

2021

Completed Phase 3

~960

Defactinib

2013

Completed Phase 1

~60

0 / 6Eligibility criteria met

Find a Location

Who is running the clinical trial?

University of UtahLead Sponsor

1,102 Previous Clinical Trials

1,779,228 Total Patients Enrolled

15 Trials studying Melanoma

1,318 Patients Enrolled for Melanoma

Verastem, Inc.Industry Sponsor

38 Previous Clinical Trials

2,565 Total Patients Enrolled

1 Trials studying Melanoma

13 Patients Enrolled for Melanoma

Howard Colman, MD, PhDPrincipal InvestigatorHuntsman Cancer Institute/ University of Utah

1 Previous Clinical Trials

66 Total Patients Enrolled

Frequently Asked Questions

These questions and answers are submitted by anonymous patients, and have not been verified by our internal team.

Is this medical research study currently open for enrollment?

"According to the information provided on clinicaltrials.gov, this particular clinical trial is not currently seeking participants. The initial posting date was 1/15/2024 and the most recent update occurred on 12/22/2023. However, it's worth noting that there are currently 1051 other ongoing studies actively recruiting patients at this time."

Answered by AI

Recent research and studies

clinicaltrials.govStudy

Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma

2024. "Defactinib and Avutometinib, With or Without Encorafenib, for the Treatment of Patients With Brain Metastases From Cutaneous Melanoma". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT06194929.