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BRAF Inhibitor

Immunotherapy + Targeted Therapy for Melanoma

Phase 3

Waitlist Available

Led By Michael B Atkins

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

Age >= 18 years. Because no dosing or adverse event data are currently available on the use of dabrafenib or dabrafenib + trametinib or nivolumab or nivolumab + ipilimumab therapy in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.

Age >= 18 years

Must not have

History of lymphoproliferative disorder

Other current malignancies, except specified exceptions

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing two different treatments for melanoma that cannot be removed by surgery. The first treatment is immunotherapy with monoclonal antibodies, followed by targeted therapy with dabrafenib and trametinib. The second treatment is targeted therapy with dabrafenib and trametinib, followed by immunotherapy with monoclonal antibodies. It is not yet known which treatment is more effective.

Who is the study for?

Adults with stage III-IV melanoma that can't be surgically removed and have the BRAFV600 mutation. They should not have HIV, other cancers within the last 5 years (except certain skin cancers), serious medical conditions, or be pregnant/breastfeeding. Participants must agree to use effective contraception.

What is being tested?

The trial is testing two treatment sequences for advanced melanoma: starting with ipilimumab and nivolumab (immunotherapies) followed by dabrafenib and trametinib (targeting BRAFV600 gene), versus starting with dabrafenib and trametinib followed by immunotherapies, to see which is more effective.

What are the potential side effects?

Possible side effects include immune system reactions affecting organs, infusion-related reactions from antibodies, heart issues due to targeted therapies, liver problems, skin rash, fever, fatigue, eye problems like blurred vision or dry eyes.

Eligibility Criteria

Inclusion Criteria

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

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I am 18 years old or older.

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I am 18 years old or older.

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My cancer is at an advanced stage and cannot be removed with surgery.

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My cancer has a BRAF V600 mutation confirmed by an approved test.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My melanoma cannot be removed by surgery and has been confirmed by tests.

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My melanoma has the BRAF V600 mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of disorders related to lymphocyte proliferation.

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I do not have any other cancers, except for allowed exceptions.

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I have a history of heart problems or risks.

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I am HIV positive.

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I am not using any medications or therapies that are not allowed in the study.

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I don't have issues swallowing or absorbing medications.

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I have had a blockage in the veins of my retina.

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I have an active cancer other than basal or squamous cell skin cancer.

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I have brain metastases that are currently treated and stable.

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I have lung scarring or inflammation.

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I have an autoimmune disease that could come back and affect my organs.

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

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall survival (OS) rate

Secondary study objectives

Progression-free survival (PFS)

Response rate

Toxicity rate for categorized AEs

+2 more

Other study objectives

Change in patient-reported symptoms

Genetic characteristics

Immune-related adverse events (irAE) status

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Arm D (immunotherapy)Experimental Treatment7 Interventions

IMMUNOTHERAPY INDUCTION (CYCLES 1-2): Patients receive nivolumab IV over 30-60 minutes and ipilimumab IV over 30-90 minutes on days 1 and 22. Treatment repeats every 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. IMMUNOTHERAPY MAINTENANCE (CYCLES 3-14): Patients receive nivolumab IV over 30-60 minutes on days 1, 15, and 29. Treatment repeats every 6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.

Group II: Arm C (BRAF inhibitor therapy)Experimental Treatment7 Interventions

Patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO daily on days 1-42. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.

Group III: Arm B (BRAF inhibitor therapy)Experimental Treatment7 Interventions

Patients receive dabrafenib mesylate PO BID and trametinib dimethyl sulfoxide PO daily on days 1-42. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity. Upon disease progression (or before), patients re-register and cross over to Arm D. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.

Group IV: Arm A (immunotherapy)Experimental Treatment7 Interventions

IMMUNOTHERAPY INDUCTION (CYCLES 1-2): Patients receive nivolumab IV over 30-60 minutes and ipilimumab IV over 30-90 minutes on days 1 and 22. Treatment repeats every 6 weeks for 2 cycles in the absence of disease progression or unacceptable toxicity. IMMUNOTHERAPY MAINTENANCE (CYCLES 3-14): Patients receive nivolumab IV over 30-60 minutes on days 1, 15, and 29. Treatment repeats every 6 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Upon disease progression (or before), patients re-register and cross over to Arm C. Patients also undergo CT, ECHO or MUGA, and collection of blood samples throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biospecimen Collection

2004

Completed Phase 3

~2020

Echocardiography

2013

Completed Phase 4

~11580