Ibrutinib for Refractory Melanoma

Not currently recruiting at 17 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether ibrutinib (also known as Imbruvica) can effectively treat stage IV melanoma, a type of skin cancer that hasn't responded to other treatments. Ibrutinib blocks certain enzymes that aid cancer cell growth. Individuals with stage IV melanoma who have not found success with other treatments might be suitable for this trial. Participants will take ibrutinib daily in cycles, provided their disease does not progress and they do not experience severe side effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that ibrutinib is likely to be safe for humans?

Research has shown that ibrutinib has been tested for safety in conditions such as chronic lymphocytic leukemia (CLL). In a large study involving 616 CLL patients, ibrutinib prevented disease progression for an average of 35 months. This indicates that the treatment can be used for an extended period without the disease worsening.

In terms of safety, ibrutinib has generally been well-tolerated, though some patients have experienced side effects. These may include mild issues like diarrhea or fatigue. In some instances, more serious side effects such as bleeding or irregular heartbeats have occurred, though these are less common.

Overall, existing evidence from other studies suggests that ibrutinib is manageable in terms of safety, though patients should be aware of possible side effects. It is important to discuss any concerns with a healthcare provider when considering joining a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ibrutinib is unique because it targets a protein called Bruton's tyrosine kinase (BTK), which plays a critical role in the survival and proliferation of cancer cells. Unlike the standard melanoma treatments that often focus on inhibiting other pathways, ibrutinib's action on BTK offers a novel approach. Researchers are excited about this treatment because it has the potential to combat refractory melanoma, which is resistant to existing therapies, by disrupting cancer growth at a different molecular level. This fresh angle could lead to new hope for patients who have not responded to current options.

What evidence suggests that ibrutinib might be an effective treatment for melanoma?

Research has shown that ibrutinib, which participants in this trial will receive, can slow the growth of melanoma cells. In lab studies, ibrutinib reduced the spread of cancer cells, particularly in those with certain enzyme levels. Although primarily used for other cancer types, ibrutinib shows promise for treating skin melanoma by blocking enzymes necessary for cancer cell growth. Early tests in other conditions showed positive results, suggesting that ibrutinib might benefit patients with melanoma unresponsive to other treatments. This makes it a hopeful option for those with advanced melanoma. ^{1 3 4 6 7}

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

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8025369/

Targeting the IL-2 Inducible Kinase in Melanoma; A Phase ... This report shows that ibrutinib has a significant effect in suppressing proliferation in melanoma cell lines that at least express intermediate levels of ITK ...

2. withpower.com withpower.com/trial/ibrutinib-for-refractory-melanoma-d11c6

Ibrutinib for Refractory Melanoma · Info for Participants 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.

3. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3801/537228/Real-world-survival-outcomes-in-first-line

Real-world survival outcomes in first-line ibrutinib-treated ... Real-world studies have also confirmed the benefit of 1L ibrutinib treatment; specifically, real-world OS (rwOS) rates were reported to be 89% ...

4. bloodresearch.or.kr bloodresearch.or.kr/journal/view.html?uid=2650&vmd=Full

A retrospective analysis of ibrutinib outcomes in relapsed ... During a median follow-up of 46.0 months, the response rate to ibrutinib was 69%, with 12 CRs and 8 partial responses. Disease progression (54.8 ...

5. news.abbvie.com news.abbvie.com/2017-06-05-Long-Term-IMBRUVICA-R-ibrutinib-Efficacy-and-Safety-Data-at-ASCO-2017-Show-Sustained-Survival-Rates-in-Up-to-Four-Years-in-Previously-Treated-Chronic-Lymphocytic-Leukemia-Small-Lymphocytic-Lymphoma-CLL-SLL-Patients-Including-Those-with-High-Ris

Long-Term IMBRUVICA® (ibrutinib) Efficacy and Safety ... Data show 59 percent progression free survival and 74 percent overall survival in CLL/SLL patients treated with IMBRUVICA, with high-risk patients trending to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5927982/

Toxicities and outcomes of 616 ibrutinib-treated patients in ... In the largest reported series of ibrutinib-treated CLL patients so far, we found that the median progression-free survival was 35 months. Interestingly, this ...

7. jnj.com jnj.com/media-center/press-releases/new-data-demonstrate-long-term-benefit-of-imbruvica-ibrutinib-as-first-line-treatment-for-high-risk-chronic-lymphocytic-leukemia

New Data Demonstrate Long-Term Benefit of IMBRUVICA ... Data presented showed that high-risk patients receiving IMBRUVICA® significantly prolonged TTNT compared to those receiving CIT.3 · IMBRUVICA® ...