Tucatinib + Radiation for Breast Cancer

Recruiting at 1 trial location

Overseen By Dr. Katarzyna Jerzak

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Strong CYP2C8 inhibitors

Disqualifiers: Prior WBRT, Gastrointestinal diseases, 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

Compensation: Varies

Number of Visits: 9

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with HER2+ metastatic breast cancer that has spread to the brain or spine. The study aims to evaluate the safety and effectiveness of a drug mix, including tucatinib (a targeted therapy) and trastuzumab, combined with radiation therapy. It seeks participants diagnosed with HER2+ breast cancer showing signs of the disease in the brain or spine. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. Specifically, you must have completed any prior chemotherapy, immunotherapy, or endocrine therapy at least 14 days before joining the study. Additionally, you cannot use strong CYP2C8 inhibitors or strong CYP3A4 or CYP2C8 inducers close to the start of the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of tucatinib, trastuzumab, and capecitabine is generally well-tolerated by patients with HER2-positive metastatic breast cancer. Studies have found that this combination helps patients live longer without their cancer worsening. It is approved for use in patients with HER2-positive breast cancer, regardless of whether the cancer has spread to the brain, indicating its safety.

Some side effects have been reported, but they are usually manageable. Common side effects may include diarrhea, nausea, or tiredness, while serious side effects are less common. Since this study is in its second phase, the treatment has already been tested on a larger group of people, demonstrating researchers' confidence in its basic safety. Always consult a healthcare provider to understand the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of tucatinib, trastuzumab, and capecitabine for HER2+ metastatic breast cancer with leptomeningeal disease because it targets cancer more precisely. Unlike standard treatments that often rely on broader chemotherapy approaches, tucatinib specifically blocks the HER2 protein, which is overexpressed in some breast cancers, potentially leading to fewer side effects. This combination is also being tested with radiotherapy, aiming to improve outcomes in the brain and spinal regions, areas notoriously difficult to treat with conventional therapies. By focusing on these targeted mechanisms, the treatment offers hope for more effective and less toxic management of this challenging condition.

What evidence suggests that this trial's treatments could be effective for HER2+ metastatic breast cancer with leptomeningeal disease?

Research has shown that combining tucatinib, trastuzumab, and capecitabine effectively treats HER2-positive metastatic breast cancer. In this trial, participants will receive this combination along with brain and/or spinal radiotherapy. When used together, tucatinib, trastuzumab, and capecitabine significantly improve progression-free survival, allowing patients to live longer without their cancer worsening. Studies have found that this combination works well even for patients whose cancer has spread to the brain, a challenging condition to treat. Trastuzumab is also known to extend the overall survival of patients with HER2-positive metastatic breast cancer. This evidence strongly suggests that this treatment combination could be effective for those with HER2-positive metastatic breast cancer and cancer that has spread to the membranes around the brain and spinal cord. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with HER2+ metastatic breast cancer that has spread to the brain or spine. Participants should have an ECOG performance status of ≤2, indicating they can perform daily activities with some limitations. They must be two weeks past their last cancer therapy and recovered from its side effects (except mild neuropathy or hair loss). Heart function needs to be normal.

Inclusion Criteria

My heart's pumping ability is within the normal range.

I am able to get out of my bed or chair and move around.

My cancer has spread to my brain or spine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy

Participants receive brain and/or spinal radiotherapy (XRT)

6 weeks

Weekly visits for radiotherapy sessions

Systemic Therapy

Participants receive systemic therapy with tucatinib, trastuzumab, and capecitabine

Up to 36 months

Every 3 weeks for treatment cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 100 months

Every 6 weeks for assessments

What Are the Treatments Tested in This Trial?

Interventions

• Brain & Spinal Radiation
• Trastuzumab
• Tucatinib

Trial Overview The study tests the safety and effectiveness of combining radiation therapy for the brain/spine with systemic therapy using Tucatinib, Capecitabine, and Trastuzumab in patients with HER2+ metastatic breast cancer having leptomeningeal disease (LMD).

How Is the Trial Designed?

Group I: Tucatinib, Transtuzumab, Capecitabine Experimental Treatment 4 Interventions

Tucatinib, Trastuzumab and Capecitabine With Brain and/or Spinal Radiotherapy (XRT) in Patients With HER2+ Metastatic Breast Cancer and Leptomeningeal Disease.

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

Approved in European Union as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in United States as Herceptin for:

• Adjuvant treatment of HER2-positive breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Canada as Herceptin for:

• Early breast cancer
• Metastatic breast cancer
• Advanced gastric cancer

Approved in Japan as Herceptin for:

• Breast cancer
• Gastric cancer

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Viatris Inc.

Industry Sponsor

Trials

11

Recruited

5,600+

Biocon Biologics

Collaborator

Trials

1

Recruited

30+

Seagen Inc.

Industry Sponsor

Trials

212

Recruited

73,800+

Founded

1997

Headquarters

Bothell, USA

Known For

Antibody-Drug Conjugates

Top Products

Adcetris (brentuximab vedotin), Tukysa (tucatinib), Padcev (enfortumab vedotin-ejfv), Tivdak (tisotumab vedotin-tftv)

Dr. Roger Dansey

Seagen Inc.

Chief Medical Officer since 2018

MD from University of Witwatersrand

David R. Epstein

Seagen Inc.

Chief Executive Officer since 2022

BSc in Pharmacy from Rutgers University, MBA from Columbia University

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Targeting HER2 with trastuzumab enhances the effectiveness of radiation therapy in breast cancer cells, particularly in those with high HER2 levels, by increasing apoptosis in a HER2-dependent manner.

The study suggests that the phosphatidylinositol 3-kinase (PI3-K) pathway plays a crucial role in this radiosensitization effect, as inhibiting this pathway significantly increased the sensitivity of HER2-overexpressing breast cancer cells to radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitization of breast cancer cells to radiation by trastuzumab. Liang, K., Lu, Y., Jin, W., et al.[2022]

In a Phase II trial involving 19 patients with HER2-positive breast cancer, the combination of trastuzumab and radiotherapy was well tolerated, with manageable side effects and no cases of symptomatic cardiac dysfunction reported.

The treatment showed promising efficacy, with 43% of patients achieving a substantial pathologic response after surgery, significantly higher than a comparison group, and a median overall survival of 39 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitization of chemotherapy-refractory, locally advanced or locally recurrent breast cancer with trastuzumab: a phase II trial. Horton, JK., Halle, J., Ferraro, M., et al.[2022]

Trastuzumab (Herceptin) is effective for treating advanced breast cancer in patients with HER-2/neu gene amplification or protein overexpression, showing improved survival when combined with chemotherapy agents like paclitaxel or docetaxel.

The success of Herceptin therapy is highly dependent on accurately identifying patients with HER-2/neu overexpression, and careful management is needed due to potential cardiac toxicity when used with certain chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives of immunotherapy in metastatic breast cancer. Lüftner, D., Pollmann, D., Schildhauer, S., et al.[2015]

HER2-positive breast cancer, which makes up 20-25% of breast cancers, has seen improved management and outcomes over the last decade with the introduction of trastuzumab, a monoclonal antibody targeting the HER2 receptor.

Despite the effectiveness of trastuzumab, resistance can develop, leading to the exploration of additional therapies such as lapatinib, pertuzumab, and neratinib, which are being investigated for their potential benefits in patients who progress under trastuzumab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Management of metastatic HER2-positive breast cancer: present and future]. Guiu, S., Coudert, B., Favier, L., et al.[2019]

In a study of 1,503 patients with early-stage HER-2-positive breast cancer, concurrent treatment with trastuzumab and radiotherapy did not lead to an increase in acute adverse events after surgery, indicating a favorable safety profile.

While there was a higher incidence of leukopenia in patients receiving trastuzumab compared to those who did not, the overall rates of cardiac events remained low and stable, suggesting that the combination treatment is safe in terms of cardiac health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. Halyard, MY., Pisansky, TM., Dueck, AC., et al.[2022]

In a phase II trial, tucatinib combined with trastuzumab and capecitabine significantly improved overall survival and progression-free survival in patients with locally advanced or metastatic HER2-positive breast cancer who had previously undergone treatment.

The combination therapy also showed enhanced progression-free survival specifically in patients with brain metastases, indicating its potential effectiveness in a challenging subset of breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib Impresses in Breast Cancer. [2020]

Combining anti-HER2 monoclonal antibodies like trastuzumab and pertuzumab with radiation therapy appears to be safe, showing no significant increase in toxicity based on the reviewed literature.

However, caution is advised when combining radiation with tyrosine kinase inhibitors (like lapatinib and tucatinib) and certain antibody-drug conjugates, as the safety of these combinations is not well established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction between Radiation Therapy and Targeted Therapies in HER2-Positive Breast Cancer: Literature Review, Levels of Evidence for Safety and Recommendations for Optimal Treatment Sequence. Debbi, K., Grellier, N., Loganadane, G., et al.[2023]

In a study of 48 Japanese patients with early-stage HER2-positive breast cancer, adjuvant trastuzumab treatment showed a low incidence of cardiac events, suggesting it is a safe option for this population.

The disease-free survival rates were high, with 97.5% at 1 year and 92.9% at 2 years, indicating that trastuzumab is effective in preventing cancer recurrence in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac safety of trastuzumab as adjuvant treatment for Japanese patients with early breast cancer. Ishihara, M., Mukai, H., Nagai, S., et al.[2022]

Tucatinib, at a recommended phase 2 dose of 300 mg twice daily, demonstrated acceptable safety with manageable side effects, including diarrhea and nausea, in a study of 60 patients with HER2-positive breast cancer.

The combination of tucatinib with capecitabine or trastuzumab showed promising anti-tumor activity, with an objective response rate of 83% for tucatinib plus capecitabine, indicating its potential as an effective treatment option for patients who have progressed on other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tucatinib with capecitabine and trastuzumab in advanced HER2-positive metastatic breast cancer with and without brain metastases: a non-randomised, open-label, phase 1b study. Murthy, R., Borges, VF., Conlin, A., et al.[2022]

Trastuzumab significantly improves treatment outcomes for women with HER2 positive breast cancer, as shown in four large randomized trials.

The main safety concerns associated with trastuzumab are serious infusion-related reactions and cardiotoxicity, highlighting the need to weigh the benefits against these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab in the adjuvant treatment of breast cancer. Svetlovska, D., Mardiak, J., Kristova, V.[2016]

Trastuzumab (Herceptin) has been established as the standard treatment for HER-2/neu positive breast cancer in the adjuvant setting, demonstrating significant efficacy when combined with chemotherapy in randomized trials.

Different administration schedules of trastuzumab, either concurrently with chemotherapy or sequentially after treatment, have been studied, highlighting the need to balance efficacy with potential toxicities in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[HER-2/neu positive breast cancer: how to prescribe adjuvant trastuzumab (Herceptin)?]. Belkacémi, Y., Gligorov, J., Mauriac, L., et al.[2015]

Citations

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Efficacy of Trastuzumab Deruxtecan in HER2-Positive and ... HER2-positive patients experienced longer PFS compared to HER2-low patients (not reached vs 9.0 months). Among HER2-low patients, liver ...

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Trastuzumab deruxtecan for the treatment of patients with ... T-DXd has promising effectiveness in heavily pre-treated HER2+ metastatic breast cancer patients with BM and LMC. The incidence and median onset time of ILD ...

3. nature.com nature.com/articles/s41598-025-07191-3

Survival outcomes among patients with breast cancer and ... The median OS of patients with LMD was 5.5 months (Supp Fig. 2). Patients with HER2-positive disease demonstrated markedly longer OS compared to ...

4. esmoopen.com esmoopen.com/article/S2059-7029(25)01380-8/fulltext

Effectiveness of post-trastuzumab deruxtecan treatments ... Effectiveness of post-trastuzumab deruxtecan treatments and incidence of interstitial lung disease in HER2-positive metastatic breast cancer: a ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e13023

Efficacy and safety of trastuzumab deruxtecan in HER2+ ... Our study supports the efficacy and safety of T-DXd in India in a real-world clinical setting with results being consistent across published literature.

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa1914609

Tucatinib, Trastuzumab, and Capecitabine for HER2 ... Adding tucatinib to trastuzumab and capecitabine resulted in better progression-free survival and overall survival outcomes than adding placebo.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.2018

TBCRC049 phase 2 study results. The combination of tucatinib-trastuzumab-capecitabine is approved for patients with metastatic HER2+ breast cancer, with or without brain metastases.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05253911

Tucatinib in Patients With Locally Advanced or Metastatic ... The objective of this non-interventional study (NIS) is to evaluate tucatinib (TUKYSA®) combined with trastuzumab and capecitabine in adult patients with ...

9. pfizer.com pfizer.com/news/press-release/press-release-detail/tukysa-combination-significantly-improves-progression-free

TUKYSA Combination Significantly Improves Progression ... TUKYSA Combination Significantly Improves Progression-Free Survival as First-Line Maintenance in HER2+ Metastatic Breast Cancer in HER2CLIMB-05 ...

10. conference-correspondent.com conference-correspondent.com/highlights/sabcs/safety-and-efficacy-of-a-tucatinib-trastuzumab-capecitabine-combination-treatment-for-leptomeningeal-metastases-in-her2-positive-breast-cancer

Safety and Efficacy of a Tucatinib-Trastuzumab ... Tucatinib-trastuzumab-capecitabine combination therapy has been shown to double the overall survival in patients with HER2-positive breast cancer with ...