Chemoradiation for High-risk Breast Cancer

(Breast53 Trial)

Overseen By Janowski

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Virginia

Must not be taking: Endocrine therapy

Disqualifiers: Lupus, Scleroderma, Metastatic disease, others

Stay on Your Current Meds You can continue your current medications while participating

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: Unknown

Duration: Approximately 6 months

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a treatment for individuals with high-risk breast cancer who still have cancer cells after initial chemotherapy and surgery. It examines the effectiveness of combining chemotherapy pills or infusions with radiation and their impact on the immune system. Participants will receive one of two treatments: T-DM1 infusions (a type of targeted therapy) with radiation or capecitabine pills (a chemotherapy drug) with radiation, depending on their cancer specifics. This trial suits those with stage I-IIIB breast cancer who have already undergone chemotherapy and surgery and are candidates for additional treatment. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires participants to stop taking endocrine therapy if they are currently on it. If you are taking warfarin and plan to receive capecitabine, your anticoagulant management will need to be assessed before starting treatment.

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

Previous studies have shown that T-DM1 effectively treats HER2-positive breast cancer. Although T-DM1 can cause side effects, it is generally considered safe. About 26% of patients experienced side effects, but these were manageable.

Research on capecitabine shows it is safe for HER2-negative breast cancer. It has improved survival rates and is well-tolerated by most patients. Some studies suggest it can reduce the risk of cancer returning by 30% or more.

Both treatments are used alongside radiation. Safety data from past studies indicate these treatments are generally well-tolerated, and doctors can manage the known side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for high-risk breast cancer because they bring innovative approaches to tackling the disease. T-DM1, also known as trastuzumab emtansine, combines targeted therapy with chemotherapy, delivering a potent drug directly to cancer cells while sparing healthy ones. This dual-action mechanism is different from traditional chemotherapy, which affects both cancerous and healthy cells. Meanwhile, capecitabine offers a convenient oral chemotherapy option that turns into a cancer-fighting drug once inside the body, potentially reducing side effects often seen with intravenous chemotherapy. These treatments aim to provide more effective, targeted, and manageable options for patients with specific breast cancer profiles.

What evidence suggests that this trial's treatments could be effective for high-risk breast cancer?

Research has shown that T-DM1 (trastuzumab emtansine) can effectively treat HER2-positive breast cancer. It reduces the risk of cancer spreading or causing death by about half compared to other treatments. T-DM1 also helps patients live longer and shrinks tumors more effectively than some other drug combinations. In this trial, participants with HER2-positive breast cancer will receive T-DM1 along with radiation.

For capecitabine, studies have found it benefits patients with HER2-negative breast cancer who still have cancer after initial treatments. It reduces the chance of the cancer returning or causing death by 30% or more. Participants with HER2-negative breast cancer in this trial will receive capecitabine along with radiation. Both treatments, when combined with radiation, show promise in improving outcomes for patients with high-risk breast cancer. ^{3 4 5 6 7}

Who Is on the Research Team?

Einsley Janowski, Md, PhD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults over 18 with stage I-IIIB breast cancer who've had neoadjuvant chemotherapy and surgery but still have residual disease. They must be able to follow the study plan, start radiation within 12 weeks post-surgery, and have good organ function. Those pregnant, lactating, or with certain medical conditions like severe allergies to treatment components or infections are excluded.

Inclusion Criteria

Agreement to adhere to Lifestyle Considerations throughout study duration

I've had at least 3 rounds of chemo and surgery for my breast cancer.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I am currently on IV antibiotics for a bacterial or fungal infection.

I have a pacemaker on the side of my body that needs treatment.

You are allergic to the ingredients in capecitabine or T-DM1.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant chemoradiation therapy with capecitabine or T-DM1 depending on Her2 status, along with radiation to the breast or chest wall and lymph nodes

Approximately 6 months

Regular visits for treatment and blood draws

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment, including lab tests and surveys

1 year

Periodic visits for assessments and surveys

What Are the Treatments Tested in This Trial?

Interventions

• Capecitabine
• External Beam Radiation Therapy 0
• External Beam Radiation Therapy 1
• T-DM1

Trial Overview The study tests adjuvant chemoradiation's safety and effectiveness in high-risk breast cancer patients after surgery. It involves T-DM1 (a targeted therapy), Capecitabine (chemotherapy), and External Beam Radiation Therapy to see how they work together against remaining cancer cells.

How Is the Trial Designed?

Group I: Her2/neu positive and lymph node positive Experimental Treatment 2 Interventions

T-DM1/ trastuzumab emtansine infusion along with radiation to the breast or chest wall and lymph nodes

Group II: Her2/neu positive and lymph node negative Experimental Treatment 2 Interventions

T-DM1/trastuzumab emtansine infusion along with radiation to the whole breast or chest wall

Group III: Her2/neu negative and lymph node positive Experimental Treatment 2 Interventions

oral capecitabine twice per day along with radiation to the breast or chest wall and lymph nodes

Group IV: Her2/neu negative and lymph node negative Experimental Treatment 2 Interventions

oral capecitabine twice per day along with radiation to the whole breast or chest wall

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

The WSG-ADAPT-TP trial showed that 12 weeks of neoadjuvant therapy with T-DM1, with or without endocrine therapy, resulted in similar 5-year invasive disease-free survival (iDFS) and overall survival rates among patients with HR+/HER2+ early breast cancer, indicating its efficacy without the need for conventional chemotherapy.

Pathologic complete response (pCR) was linked to improved survival rates, and among patients achieving pCR, those who did not receive adjuvant chemotherapy had comparable iDFS rates, suggesting that de-escalated therapy can be safe and effective for certain patients based on biomarker profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De-Escalated Neoadjuvant Trastuzumab-Emtansine With or Without Endocrine Therapy Versus Trastuzumab With Endocrine Therapy in HR+/HER2+ Early Breast Cancer: 5-Year Survival in the WSG-ADAPT-TP Trial. Harbeck, N., Nitz, UA., Christgen, M., et al.[2023]

In the phase III KAITLIN study involving 1846 adults with high-risk HER2-positive early breast cancer, replacing taxanes and trastuzumab with trastuzumab emtansine (T-DM1) did not significantly improve invasive disease-free survival compared to the standard treatment of trastuzumab plus pertuzumab with chemotherapy.

While both treatment regimens showed favorable outcomes, the completion rate for the T-DM1 group was lower (65.0%) due to more laboratory abnormalities, indicating potential safety concerns despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer: The Phase III KAITLIN Study. Krop, IE., Im, SA., Barrios, C., et al.[2023]

In a study of 325 HER2-positive metastatic breast cancer patients, the objective response rate (ORR) for treatments following trastuzumab emtansine (T-DM1) was 22.8%, indicating limited effectiveness of post-T-DM1 therapies.

The median overall survival (OS) for patients after T-DM1 was 23.7 months, suggesting that while some patients may benefit, there is a need for further research into more effective treatment options beyond T-DM1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B). Yokoe, T., Kurozumi, S., Nozawa, K., et al.[2021]

Black men with prostate cancer had higher rates of treatment noncompletion when receiving conventional external-beam radiation therapy compared to White men, but this disparity was not observed with shorter radiation regimens like stereotactic body radiotherapy (SBRT) or moderate hypofractionation (mEBRT).

For women with breast cancer, shorter hypofractionated external-beam radiation therapy (hEBRT) was associated with lower treatment noncompletion rates compared to conventional therapy, yet Black women were less likely to receive hEBRT despite its increasing availability and potential benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter Radiation Regimens and Treatment Noncompletion Among Patients With Breast and Prostate Cancer in the United States: An Analysis of Racial Disparities in Access and Quality. Dee, EC., Taunk, NK., Chino, FL., et al.[2023]

External beam radiotherapy (EBRT) for loco-regional prostate cancer shows comparable 10-year survival rates to radical prostatectomy, with survival rates of 90-95% for T1, 60-70% for T2, and 50-60% for T3 stages, indicating its effectiveness as a treatment option.

Advancements in radiotherapy techniques, such as 3D-conformal RT and intensity-modulated RT (IMRT), allow for higher radiation doses to be delivered to the tumor while minimizing damage to surrounding tissues, and the use of cytoprotection with amifostine may help reduce radiation side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

External beam radiotherapy for prostate cancer: current position and trends. Koukourakis, MI., Touloupidis, S.[2006]

In a study of 229 patients with localized prostate cancer, those receiving external-beam radiotherapy (EBRT) alone had better biochemical relapse-free survival (81%) compared to those receiving EBRT combined with high-dose-rate brachytherapy (HDR-BT) (67%), suggesting that EBRT alone may be more effective.

The study also found that patients receiving EBRT with HDR-BT experienced significantly higher rates of late gastrointestinal complications (9.2% vs. 24.8%), indicating that while HDR-BT may offer some benefits, it also comes with increased risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness and side effects of conformal external beam radiotherapy combined with high-dose-rate brachytherapy boost compared to conformal external beam radiotherapy alone in patients with prostate cancer. Smolska-Ciszewska, B., Miszczyk, L., Białas, B., et al.[2018]

In a study of 32 patients receiving External Beam Radiotherapy (EBRT) for bone metastases, 41% experienced a pain flare, which is defined as a significant increase in pain or analgesia intake, with a median duration of 3 days.

The incidence and duration of pain flare observed in this study align with findings from international studies, indicating that pain flare is a common side effect of EBRT for bone metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation into the incidence of pain flare in patients undergoing radiotherapy for symptomatic bone metastases. Goldfinch, R., White, N.[2018]

In a study of 45 breast cancer patients undergoing stereotactic radiosurgery (SRS) for brain metastases, 22.2% developed clinically significant radionecrosis (CSRN), with a striking 39.1% of those receiving trastuzumab emtansine (T-DM1) experiencing this complication compared to only 4.5% of those not receiving T-DM1.

The use of T-DM1 was linked to a 13.5-fold increase in the risk of CSRN, likely due to its targeting of reactive astrocytes, which enhances radiation-induced damage and swelling, suggesting that caution is needed when combining T-DM1 with SRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4. Stumpf, PK., Cittelly, DM., Robin, TP., et al.[2020]

The KAMILLA study, involving 2002 patients with HER2-positive advanced breast cancer, demonstrated that trastuzumab emtansine (T-DM1) is a safe and tolerable treatment, with 93% of patients experiencing adverse events, primarily mild to moderate in severity.

The study reported a median progression-free survival of 6.9 months and a median overall survival of 27.2 months, indicating that T-DM1 is an effective option for patients who have previously undergone multiple lines of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of trastuzumab emtansine (T-DM1) in patients with HER2-positive advanced breast cancer: Primary results from the KAMILLA study cohort 1. Montemurro, F., Ellis, P., Anton, A., et al.[2020]

Trastuzumab emtansine (Kadcyla) has been authorized for use in women with HER-2 positive metastatic breast cancer after taxane and trastuzumab treatment failure, showing an overall survival benefit of about 6 months compared to capecitabine + lapatinib in a trial of 991 patients.

While trastuzumab emtansine is associated with serious side effects like hepatic toxicity and peripheral neuropathy, it appears to be less toxic to skin and mucous membranes compared to the capecitabine + lapatinib combination, highlighting the need for careful consideration of its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine. An inadequately assessed combination of two cytotoxic drugs. [2019]

Trastuzumab emtansine is an effective treatment for HER2-positive breast cancer, showing significant improvements in overall survival compared to lapatinib plus capecitabine in a phase III study, with a maximum tolerated dose established at 3.6 mg/kg.

The treatment has a favorable safety profile, with minimal systemic toxicities and a low incidence of adverse events typically associated with chemotherapy, such as cardiotoxicity, making it a promising option for patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The success story of trastuzumab emtansine, a targeted therapy in HER2-positive breast cancer. Diéras, V., Bachelot, T.[2021]

A study of 113,719 men with intermediate- or high-risk prostate cancer showed that combining external beam radiation therapy (EBRT) with a brachytherapy boost (BB) is associated with improved overall survival, indicated by a hazard ratio of 0.71 for intermediate-risk and 0.73 for high-risk patients.

Despite the survival benefits, the use of brachytherapy has significantly declined from 2004 to 2013, with only 12.5% of intermediate-risk and 10.8% of high-risk patients receiving BB by 2013, highlighting a concerning trend in treatment choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brachytherapy boost for prostate cancer: Trends in care and survival outcomes. Glaser, SM., Dohopolski, MJ., Balasubramani, GK., et al.[2018]

Two patients with HER2-positive breast cancer experienced significant enlargement of radiation necrosis after starting T-DM1 therapy, suggesting a potential adverse effect of this targeted treatment on previously irradiated brain tissue.

These cases emphasize the importance of careful monitoring for patients receiving T-DM1 after stereotactic radiosurgery, as the combination may lead to worsening symptoms and necessitate surgical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases. Mitsuya, K., Watanabe, J., Nakasu, Y., et al.[2019]

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Efficacy and Safety of Capecitabine for Triple-Negative ... The lower dosage and higher frequency of capecitabine combined with adjuvant chemotherapy demonstrated a better survival outcome. Data ...