What is the mechanism of action of this treatment?

Ibrutinib, a BTK inhibitor, works by blocking Bruton's tyrosine kinase, a protein essential for the survival and proliferation of certain cancer cells, thereby inhibiting tumor growth. Trastuzumab, a HER2 receptor inhibitor, targets the HER2 protein, which is overexpressed in some breast cancers, leading to reduced tumor growth and survival. These treatments are crucial for breast cancer patients as they offer targeted therapy options that can be more effective and potentially less toxic than traditional chemotherapy. Additionally, understanding these mechanisms helps in developing strategies to overcome drug resistance, improving patient outcomes.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as Ibrutinib (BTK Inhibitor) and Trastuzumab (HER2 Receptor Inhibitor), have distinct side effect profiles. Ibrutinib can cause neutropenia, thrombocytopenia, atrial fibrillation, hypertension, and bleeding-related events. Trastuzumab is associated with cardiotoxicity, infusion-related reactions, and potential pulmonary toxicity. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for breast cancer, particularly targeting the HER2 receptor. Trastuzumab, a monoclonal antibody that targets the HER2 receptor, has been a cornerstone in the treatment of HER2-positive breast cancer. It is often used in combination with chemotherapy agents and other targeted therapies like pertuzumab and ado-trastuzumab emtansine (T-DM1). While BTK inhibitors like Ibrutinib are primarily used in hematologic malignancies, their combination with HER2 inhibitors like Trastuzumab is being explored in clinical trials to assess efficacy in HER2-amplified metastatic breast cancer.

What other types of research exist?

For breast cancer patients considering treatment in 2024, promising novel alternatives to Ibrutinib and Trastuzumab include: 1) Ribociclib, a CDK4/6 inhibitor, which has shown efficacy in combination with other agents for HR+ advanced breast cancer. 2) Alpelisib, a PI3K inhibitor, which has been studied in combination with fulvestrant for HR+ advanced breast cancer. These alternatives target different pathways but have demonstrated potential in recent clinical trials.

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Bruton's Tyrosine Kinase (BTK) Inhibitor

Ibrutinib + Trastuzumab for Breast Cancer

Phase 1 & 2

Waitlist Available

Led By Joyce O'Shaughnessy, MD

Research Sponsored by US Oncology Research

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

Histologic or cytologic confirmation of HER2-amplified breast cancer according to most recent biopsy (local testing permitted)

Must not have

Unwilling or unable to participate in all required study evaluations and procedures

Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination of ibrutinib (a pill) and trastuzumab (an IV drug) in patients with HER2-amplified Metastatic Breast Cancer that has worsened after previous treatment. Ibrutinib blocks proteins that help cancer grow, while trastuzumab helps the immune system attack cancer cells. Trastuzumab has been widely used in the treatment of HER2-positive breast cancer and has shown significant efficacy in combination with other therapies.

Who is the study for?

This trial is for women aged 18 or older with HER2-amplified metastatic breast cancer that worsened after T-DM1 therapy. Participants can have had up to four prior chemotherapy treatments, must not be pregnant, and agree to use two effective birth control methods. They should have good heart function (LVEF ≥ 50%), adequate blood counts, liver and kidney function, and an ECOG performance status of 0-2.

What is being tested?

The study tests different doses of Ibrutinib (560 mg, 840 mg, or 420 mg daily) combined with Trastuzumab administered intravenously. It aims to find the highest dose patients can take without serious side effects in those who've previously been treated with ado-trastuzumab emtansine for metastatic breast cancer.

What are the potential side effects?

Possible side effects include bleeding disorders due to Ibrutinib's effect on blood clotting; digestive issues from swallowing capsules; potential heart problems; risk of infection; fatigue; nausea; diarrhea; rash; muscle spasms and bone pain.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself and am up and about more than half of my waking hours.

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My latest biopsy confirms I have HER2-amplified breast cancer.

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I have had 4 or fewer (Phase I) / 3 or fewer (Phase II) chemotherapy treatments for metastatic breast cancer.

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I am a woman aged 18 or older.

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My cancer worsened within 6 months after finishing TDM1 therapy.

Exclusion Criteria

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

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I am willing and able to follow all study requirements.

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I cannot swallow pills or have serious digestive system issues.

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I haven't had chemotherapy in the last 21 days.

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I do not have any ongoing infections that aren't under control.

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I have not had major surgery within the last 4 weeks.

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I am currently taking warfarin or similar blood thinners.

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I haven't taken strong CYP3A inhibitors in the last 7 days.

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I understand the study's risks and can sign the consent form.

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I finished treatment for an infection less than 14 days ago.

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My brain cancer has not been treated or is not under control.

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I have no lasting side effects from previous cancer treatments.

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I have a serious heart condition that is currently causing symptoms.

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My liver disease is moderate to severe.

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I have a bleeding disorder or hemophilia.

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I have a history of HIV or active hepatitis B or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase I: Maximum Tolerated Dose

Phase II: Clinical Benefit Rate

Secondary study objectives

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of ibrutinib plus trastuzumab.

Median Overall Survival

Median Progression-free Survival

+3 more

Other study objectives

Cytokine Gene Expression Analysis

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Trastuzumab plus Ibrutinib 840 mgExperimental Treatment2 Interventions

If no patients in 560 mg arm have DLTs, this arm will be opened in Phase I to see how this higher dose is tolerated.

Group II: Trastuzumab plus Ibrutinib 560 mgExperimental Treatment2 Interventions

In Phase I, starting dose of Ibrutinib will be 560 mg orally per day. 3 patients will be enrolled first. If none of these have DLTs, 3 new patients will be enrolled at the next higher Ibrutinib dose level (840 mg orally per day). If 1 of these 3 patients have a DLT, expand this arm to 6 patients. If 2 or more of these 6 patients have a DLT, enroll 3 patients in lower dose lever (420 mg).

Group III: Trastuzumab plus Ibrutinib 420 mgExperimental Treatment2 Interventions

If 2 or more patients in 560 mg arm have DLTs, this arm will be opened in Phase I to see how this lower dose is tolerated.

Group IV: Phase II- Trastuzumab plus Maximum Tolerated DoseExperimental Treatment1 Intervention

Maximum tolerated dose from Phase I will be used here in Phase II.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Trastuzumab

2014

Completed Phase 4

~5190

Ibrutinib 560 mg

2019

Completed Phase 4

~80

Ibrutinib 420 mg

2019

Completed Phase 4

~80

0 / 20Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Ibrutinib, a BTK inhibitor, works by blocking Bruton's tyrosine kinase, a protein essential for the survival and proliferation of certain cancer cells, thereby inhibiting tumor growth. Trastuzumab, a HER2 receptor inhibitor, targets the HER2 protein, which is overexpressed in some breast cancers, leading to reduced tumor growth and survival. These treatments are crucial for breast cancer patients as they offer targeted therapy options that can be more effective and potentially less toxic than traditional chemotherapy. Additionally, understanding these mechanisms helps in developing strategies to overcome drug resistance, improving patient outcomes.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Ibrutinib in Gynecological Malignancies and Breast Cancer: A Systematic Review.Pharmacokinetic and pharmacodynamic evaluation of panitumumab in the treatment of colorectal cancer.