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Protein Kinase Inhibitor

Navitoclax + Dabrafenib + Trametinib for Melanoma

Phase 1 & 2

Waitlist Available

Led By Ryan J Sullivan

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

Patients must have histologically confirmed, BRAF-mutant (V600E/K) melanoma (molecularly confirmed using validated, commercially available assay performed in a Clinical Laboratory Improvement Act [CLIA]-approved laboratory) that is metastatic or unresectable and for which standard curative measures do not exist or are no longer effective

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam

Must not have

Patients who have had immunotherapy, chemotherapy or radiotherapy within 14 days prior to the first dose of navitoclax, or prior systemic anti-cancer therapy (chemotherapy with delayed toxicity, extensive radiation therapy, immunotherapy, biologic therapy, or vaccine therapy) within the last 3 weeks prior to first dose of dabrafenib and/or trametinib; chemotherapy regimens without delayed toxicity within the last 2 weeks preceding the first dose of study treatment; biologics will not be allowed within 30 days prior to, or during, navitoclax administration

History of allergic reactions attributed to compounds of similar chemical or biologic composition to navitoclax, dabrafenib, or trametinib, or excipients or to dimethyl sulfoxide (DMSO)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is studying the side effects and best dose of a combination of dabrafenib, trametinib, and navitoclax to treat patients with BRAF mutant melanoma or solid tumors.

Who is the study for?

Adults with BRAF mutant melanoma that's spread or can't be surgically removed, who have good organ function and no recent significant bleeding or other serious illnesses. They must not have had certain treatments recently, agree to use non-hormonal birth control, and be able to swallow pills. Those with known allergies to the drugs being tested or similar compounds are excluded.

What is being tested?

The trial is testing a combination of three drugs: dabrafenib, trametinib, and navitoclax for advanced melanoma with a specific mutation (BRAF V600E/K). It aims to find the best dose and see how well these drugs work together in stopping cancer growth by blocking enzymes and proteins needed by cancer cells.

What are the potential side effects?

Potential side effects include fatigue, digestive issues like nausea or diarrhea, liver problems indicated by blood tests changes, skin reactions such as rash or dry skin, fever, high blood pressure, vision changes including blurred vision or reduced sharpness of vision.

Eligibility Criteria

Inclusion Criteria

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

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My melanoma is BRAF V600E/K mutant, cannot be surgically removed, and standard treatments have failed.

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I have a tumor that can be measured with scans or exams.

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

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I can take pills and don't have major gut issues affecting drug absorption.

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I am 18 years old or older.

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My kidney function is normal or only slightly reduced.

Exclusion Criteria

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

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I haven't had cancer treatments like immunotherapy or chemotherapy in the last 14 to 30 days.

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I am allergic to navitoclax, dabrafenib, trametinib, their ingredients, or DMSO.

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I do not have any serious ongoing illnesses that would stop me from following the study's requirements.

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I am not pregnant or breastfeeding.

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I have had interstitial lung disease or pneumonitis.

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I had bleeding not caused by chemotherapy in the last year.

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I don't have ongoing major side effects from cancer treatment, except for hair loss or hormone issues.

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My high blood pressure is not controlled by medication.

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I have a condition that makes me bleed easily or I am currently experiencing significant bleeding.

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I am not taking any herbal supplements.

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I have a history of G6PD deficiency.

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I am not currently using any medication that is not allowed in the study.

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I have or am at risk for eye conditions like RVO or CSR.

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I have a history of heart problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 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

Maximal degree of tumor regression (Phase II)

Proportion of patients with a complete response (CR) (Phase II)

Recommended phase II dose of the combination of dabrafenib, trametinib, and navitoclax (Phase I)

Secondary study objectives

Objective response rate (ORR) (Phase II)

Overall survival (OS) (Phase II)

Progression free survival (PFS) (Phase II)

Other study objectives

Change in B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL-2)

Change in Ki67

Change in phosphatase and tensin homolog (PTEN) status

+4 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (dabrafenib, trametinib, and navitoclax)Experimental Treatment11 Interventions

Patients receive navitoclax PO QD days -7 to -1 of cycle 1 only. Patients also receive dabrafenib PO BID, trametinib PO QD, and navitoclax PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial.

Group II: Arm I (dabrafenib, trametinib)Experimental Treatment10 Interventions

ARM I: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO or MUGA, MRI or CT, biopsy, and collection of blood samples throughout the trial.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Biopsy

2014

Completed Phase 4

~1150

Dabrafenib

2011

Completed Phase 3

~4120