Ibrutinib for Refractory Melanoma

Recruiting at 16 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Anticoagulants, CYP3A inhibitors

Disqualifiers: Mucosal melanoma, Ocular melanoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 31

Duration: Up to 1 year

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase II trial studies how well ibrutinib works in treating patients with stage IV melanoma of the skin that has not responded to previous treatment. Ibrutinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have had chemotherapy, immunotherapy, or certain other treatments within a few weeks before starting the trial. It's best to discuss your specific medications with the trial team.

How is the drug ibrutinib unique in treating refractory melanoma?

Ibrutinib is unique in treating refractory melanoma because it targets IL-2 inducible kinase (ITK), which is highly expressed in metastatic melanomas, and it can reverse resistance to BRAF inhibitors, potentially making previously resistant tumors sensitive to treatment again. ^{1 2 3 4 5}

What data supports the effectiveness of the drug ibrutinib for treating refractory melanoma?

Research suggests that ibrutinib may help treat certain melanoma tumors that have become resistant to other treatments by reversing resistance to BRAF inhibitors, which are drugs used to target specific mutations in melanoma cells. ^{1 2 6 7 8}

Who Is on the Research Team?

Stergios J Moschos

Principal Investigator

Duke University - Duke Cancer Institute LAO

Are You a Good Fit for This Trial?

This trial is for adults with stage IV cutaneous melanoma that hasn't improved after treatment. They must have measurable disease, normal organ function, and a life expectancy over 3 months. Participants need to be able to swallow pills, agree to use contraception if applicable, and provide tissue samples if needed. Excluded are those with certain allergies, uncontrolled illnesses, recent other cancer treatments or high-dose steroids.

Inclusion Criteria

Your AST and ALT levels in your blood are not too high. If you have cancer that has spread to your liver, the levels can be a little higher but still within a certain limit.

My melanoma diagnosis was confirmed by tissue examination.

My side effects from previous cancer treatments have mostly gone away.

Exclusion Criteria

My melanoma originated in a mucous membrane or my eye.

You have had serious allergic reactions to drugs similar to ibrutinib in the past, with symptoms like difficulty breathing, lip swelling, itching, or rash.

I need regular blood transfusions due to low platelet counts.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib orally once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 1 year

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months for up to 2 years.

Up to 2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib

Trial Overview The trial tests Ibrutinib's effectiveness in treating advanced skin melanoma resistant to prior therapies by inhibiting enzymes that promote tumor cell growth. It includes laboratory biomarker analysis and pharmacological studies to understand how the drug interacts with the body.

How Is the Trial Designed?

Group I: Treatment (ibrutinib) Experimental Treatment 4 Interventions

Patients receive ibrutinib PO QD on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Vemurafenib is an effective oral treatment for patients with inoperable and metastatic melanoma that have the BRAF V600E mutation, showing improved survival rates in clinical trials.

While vemurafenib is generally effective, it can cause significant side effects, including skin cancers, joint pain, fatigue, and heart rhythm changes, necessitating regular monitoring for these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vemurafenib for the treatment of melanoma. Jordan, EJ., Kelly, CM.[2018]

Immunotherapy and targeted therapy significantly improve survival rates in patients with advanced melanoma, particularly in those with BRAF mutations, which affect about 50% of melanoma patients.

While the combination of ipilimumab and nivolumab offers the best survival outcomes, it comes with considerable toxicity, suggesting that targeted therapy may be a safer and more favorable option in specific clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Translated article] Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? Moreno-Ramírez, D., Fernández-Orland, A., Ferrándiz, L.[2023]

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

Ibrutinib is a powerful oral medication that effectively treats relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL), showing high response rates and significantly improving survival outcomes, especially in patients with poor prognostic factors like chromosome 17 deletion (del 17p).

The drug has a good safety profile, with less than 10% of patients discontinuing treatment due to side effects, making it a promising option for patients with these types of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Kim, ES., Dhillon, S.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Vemurafenib for the treatment of melanoma. [2018]

2. Spain pubmed.ncbi.nlm.nih.gov

Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? [2023]

3. England pubmed.ncbi.nlm.nih.gov

Targeting the IL-2 inducible kinase in melanoma; a phase 2 study of ibrutinib in systemic treatment-refractory distant metastatic cutaneous melanoma: preclinical rationale, biology, and clinical activity (NCI9922). [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Ibrutinib Blocks YAP1 Activation and Reverses BRAF Inhibitor Resistance in Melanoma Cells. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

[Translated article] Immunotherapy and Targeted Therapy in Patients With Advanced Melanoma and the V600 BRAF Mutation: Which One First? [2023]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. [2022]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cutaneous eruptions from ibrutinib resembling epidermal growth factor receptor inhibitor-induced dermatologic adverse events. [2023]