Immunotherapy + SBRT for Metastatic Breast Cancer

Recruiting at 4 trial locations

Overseen By Charles Ekeh, M.D

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: CDK4/6 inhibitors, Aromatase inhibitors

Must not be taking: Systemic chemotherapy, HER2-neu therapy

Disqualifiers: Connective tissue disorders, Immunodeficiency, Autoimmune disease, 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: Unknown

Duration: Up to 36 months

102 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining radiation therapy with standard treatment for metastatic breast cancer that is hormone receptor-positive and HER2-negative. The study evaluates whether adding Stereotactic Body Radiation Therapy (SBRT) to letrozole (a hormone therapy) and palbociclib (a cancer drug) improves treatment outcomes. Women with advanced breast cancer that has progressed after initial hormone therapy may qualify for this trial. Participants receive either the standard treatment or the standard treatment plus radiation to determine which is more effective. 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 does not specify if you need to stop taking your current medications, but it excludes those currently using systemic chemotherapy, endocrine therapy, or HER2-neu targeted therapy. It's best to discuss your specific medications with the trial team.

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

Research has shown that using letrozole and palbociclib together is generally safe for women with advanced breast cancer. The most common side effect, neutropenia (a low white blood cell count), can usually be managed. When combined with Stereotactic Body Radiation Therapy (SBRT), the treatment remains well-tolerated. Reports indicate that side effects are mostly mild to moderate, with no severe reactions observed. While some side effects may occur, they are not usually serious and can often be managed effectively. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for metastatic breast cancer because they combine immunotherapy with stereotactic body radiation therapy (SBRT), potentially enhancing the overall effectiveness. Unlike standard treatments like chemotherapy, which can be broadly toxic, this approach uses targeted radiation to attack cancer cells more precisely. Additionally, the combination of Letrozole and Palbociclib with SBRT is expected to improve outcomes by synchronizing hormone therapy with cell cycle inhibition, tackling cancer from multiple fronts. This innovative combination could lead to more effective and faster results, offering hope for better management of metastatic breast cancer.

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

Research has shown that using letrozole with palbociclib can effectively treat metastatic breast cancer. Studies found that patients taking both medications lived longer without their cancer worsening compared to those taking only letrozole. Specifically, the time without cancer progression was 19.3 months for the combination treatment, compared to 13.9 months for letrozole alone.

In this trial, one group of participants will receive letrozole and palbociclib, while another group will receive letrozole and palbociclib with the addition of Stereotactic Body Radiation Therapy (SBRT). Early findings suggest that combining SBRT with palbociclib and letrozole might be safe, with only minor side effects reported. SBRT uses precise, high-dose radiation to target cancer cells, which could help control the cancer's spread. While more research is needed, initial results are promising for improving treatment effectiveness. ^{2 5 6 7 8}

Who Is on the Research Team?

Silvia Formenti, M.D.

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for women over 18 with HR+ HER2- metastatic breast cancer, who can receive CDK4/6 inhibitors and aromatase inhibitors. They must have adequate organ function, no more than five measurable disease sites, and not be on certain therapies or have active infections or autoimmune diseases.

Inclusion Criteria

My cancer has spread to 5 or fewer places in my body.

I am premenopausal based on my last period, hormone therapy, or blood hormone levels.

You need to have at least 100,000 platelets per microliter of blood.

Exclusion Criteria

I have another cancer besides the one being studied that has progressed or needed treatment in the last 3 years.

I have brain metastases that are not under control.

I have a tumor larger than 5 cm.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Letrozole and Palbociclib, with I-SBRT for Arm 2, starting Letrozole alone and adding Palbociclib on day 21 after I-SBRT completion

Up to 36 months

Daily visits for I-SBRT, regular visits for medication administration

Radiation

Stereotactic Body Radiation Therapy (SBRT) is administered to each metastatic lesion, alternating daily to accommodate a 48-hour interval between fractions

≤ 12 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of ctDNA levels, ORR, adverse events, and overall survival

Up to 36 months

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole
• Palbociclib
• Stereotactic Body Radiation Therapy (SBRT)

Trial Overview The study tests if adding Stereotactic Body Radiation Therapy (SBRT) to standard first-line treatment (letrozole and palbociclib) improves outcomes in metastatic breast cancer. Participants are randomly assigned to either the combined treatment group or the standard therapy group.

How Is the Trial Designed?

Group I: ARM 2 - Letrozole and Palbociclib + I-SBRT Active Control 3 Interventions

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. Treatment may be given daily (to keep the total I-SBRT treatment time to ≤ 12 days) and lesions targeted with I-SBRT will thus be alternated each day to accommodate for the 48 hour interval between fractions.

Group II: ARM 1 - Letrozole and Palbociclib Active Control 2 Interventions

Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21.

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

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., et al.[2022]

In a study with a median follow-up of about 38 months, palbociclib combined with letrozole significantly improved progression-free survival (PFS) in women with advanced estrogen receptor-positive (ER+)/HER2-negative breast cancer, with a median PFS of 27.6 months compared to 14.5 months for the placebo group.

The treatment not only prolonged PFS but also delayed the need for chemotherapy and maintained a favorable safety profile and quality of life for patients, suggesting that palbociclib-letrozole should be the standard first-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Rugo, HS., Finn, RS., Diéras, V., et al.[2023]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

In a study of 68 patients with advanced solid tumors, the combination of stereotactic body radiotherapy (SBRT) followed by pembrolizumab showed a high one-year treated metastasis control rate of 89.5%, indicating effective tumor response regardless of whether the tumors received complete or partial radiation coverage.

The study found that treated metastasis control (TMC) was significantly associated with improved overall survival, and SBRT altered tumor gene expression by increasing immune-related genes while decreasing those related to cell cycle and DNA repair, suggesting a mechanism for enhanced immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved Survival Associated with Local Tumor Response Following Multisite Radiotherapy and Pembrolizumab: Secondary Analysis of a Phase I Trial. Luke, JJ., Onderdonk, BE., Bhave, SR., et al.[2021]

In a study of 1430 patients with hormone receptor-positive, HER2-negative metastatic breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival (20.0 months) compared to letrozole alone (11.9 months).

The combination treatment also showed a trend towards better overall survival, with a 2-year survival rate of 78.3% for the palbociclib group compared to 68.0% for those on letrozole alone, indicating its effectiveness in a real-world clinical setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness of first-line palbociclib plus letrozole versus letrozole alone for HR+/HER2- metastatic breast cancer in US real-world clinical practice. DeMichele, A., Cristofanilli, M., Brufsky, A., et al.[2022]

A survey of 27 radiation oncology centers revealed that 67% of them perform concurrent stereotactic body radiotherapy (SBRT) with targeted agents, despite limited evidence on the safety and efficacy of this combination.

There is a strong consensus against combining SBRT with antiangiogenic agents like bevacizumab, and BRAF inhibitors should be paused at least one week before SBRT to ensure patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of stereotactic radiotherapy and targeted therapy: patterns-of-care survey in German-speaking countries. Kroeze, SGC., Fritz, C., Basler, L., et al.[2020]

Stereotactic body radiotherapy (SBRT) is being increasingly considered for patients with oligometastatic breast cancer, which is defined as having 5 or fewer metastatic sites, as it may improve their prognosis through aggressive local treatment.

A survey of Canadian Medical Oncologists was conducted to understand their beliefs and opinions about the use of SBRT in this patient group, highlighting the need to identify the optimal scenarios for its implementation in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Attitudes and beliefs toward the use of stereotactic body radiotherapy in oligometastatic breast cancer: A commentary on a survey of Canadian Medical Oncologists. Donovan, E., Dhesy-Thind, S., Mukherjee, S., et al.[2020]

In the PALOMA-2 trial involving 666 postmenopausal women with ER+/HER2- advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival compared to letrozole alone, with a hazard ratio of 0.58.

Neutropenia was the most common adverse event associated with palbociclib, occurring in 95.3% of patients, but it was mostly manageable through dose modifications and did not compromise treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Diéras, V., Harbeck, N., Joy, AA., et al.[2020]

In the PALOMA-2 trial, palbociclib combined with letrozole significantly prolonged progression-free survival (PFS) in postmenopausal patients with advanced breast cancer, regardless of preexisting health conditions.

The safety profile of palbociclib plus letrozole was consistent across different preexisting conditions, with similar rates of treatment-emergent adverse events and dose modifications, indicating it is a safe option for patients with various health backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2. Gelmon, K., Walshe, JM., Mahtani, R., et al.[2021]

Palbociclib, when used with endocrine therapy, is an approved treatment for advanced breast cancer, but it is associated with common side effects like leukopenia and neutropenia.

This report highlights a rare case of acute lymphoblastic leukemia developing in a patient treated with palbociclib and letrozole, underscoring the importance of long-term monitoring for patients receiving this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute Lymphoblastic Leukemia in a Patient Treated with Letrozole and Palbociclib. Park, JH., Park, H., Kim, KH., et al.[2023]

In the phase II PALOMA-1/TRIO-18 trial involving 165 postmenopausal women with advanced ER-positive, HER2-negative breast cancer, palbociclib combined with letrozole significantly improved progression-free survival (PFS) to 20.2 months compared to 10.2 months with letrozole alone, indicating its efficacy as a first-line treatment.

While Grade 3-4 neutropenia was the most common adverse event associated with the palbociclib and letrozole combination, the incidence of neutropenia decreased over time, and most patients did not experience severe infections, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Finn, RS., Crown, JP., Ettl, J., et al.[2022]

A prospective observational study is planned with 700 postmenopausal women with metastatic breast cancer to evaluate the real-world efficacy and safety of palbociclib combined with endocrine treatments, focusing on progression-free survival across different treatment lines.

The study aims to assess not only the clinical outcomes but also the quality of life and patient-reported outcomes, addressing concerns about the increased toxicity and cost associated with palbociclib compared to standard hormone therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Cohort Study of Palbociclib Treatment in Postmenopausal Patients With Unresectable and Metastatic Hormone Receptor-Positive Breast Cancer: Study Protocol for a CSPOR-BC Palbociclib Cohort Trial. Narui, K., Ishikawa, T., Taira, N., et al.[2022]

Stereotactic body radiotherapy (SBRT) for metastatic breast cancer showed high local control rates of 89% at 1 year and 86.6% at 2 years, indicating its effectiveness in managing metastatic lesions.

Patients with oligometastases had significantly better overall survival (83.5% at 1 year) and progression-free survival (66% at 1 year) compared to those with oligoprogression or local control of dominant tumor, suggesting that SBRT can delay the need for chemotherapy or hormonal therapy in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of extra-cranial stereotactic body radiotherapy for metastatic breast cancer: Treatment indication matters. Tan, H., Cheung, P., Louie, AV., et al.[2021]

Stereotactic Body Radiation Therapy (SBRT) demonstrated excellent local control rates of 98% at 1 year and 90% at 2 and 3 years in 33 patients with oligometastatic breast cancer, indicating its efficacy in managing limited metastatic disease.

The treatment was well tolerated with no severe toxicities (G3-4), suggesting that SBRT is a safe option for patients with 1-3 lung and liver lesions who are not candidates for surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy: A promising chance for oligometastatic breast cancer. Scorsetti, M., Franceschini, D., De Rose, F., et al.[2017]

Citations

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Real-world comparative effectiveness of palbociclib plus ... This study compared real-world effectiveness of palbociclib plus letrozole versus letrozole in older patients with MBC in US clinical practice.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00137

Overall Survival With Palbociclib Plus Letrozole in ... The median OS was 53.9 months (95% CI, 49.8 to 60.8) with palbociclib plus letrozole versus 51.2 months (95% CI, 43.7 to 58.9) with placebo plus ...

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Palbociclib and Letrozole in Advanced Breast Cancer A phase 2 study showed that progression-free survival was longer with palbociclib plus letrozole than with letrozole alone in the initial ...

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Extended follow-up of palbociclib with fulvestrant or ... No significant difference in OS or PFS between fulvestrant and letrozole when combined with palbociclib was observed. Median OS was 61.8 months, and median PFS ...

5. nature.com nature.com/articles/s41523-022-00479-x

Real-world study of overall survival with palbociclib plus ... Progression-free survival (95% CI) is 19.3 (17.5–20.7) versus 13.9 (12.5–15.2) months, respectively (hazard ratio, 0.70 [95% CI, 0.62–0.78]; P < ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4924326/

Efficacy and safety of palbociclib in combination with letrozole ... Based on the data from PALOMA-1/TRIO-18, palbociclib received accelerated approval from the US FDA for use in these patients. The role of CDK 4/6 inhibition in ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8100571/

Long‐Term Pooled Safety Analysis of Palbociclib in ... This 5-year, long-term analysis demonstrated that palbociclib plus ET has a consistent and stable safety profile and is a safe treatment for patients with HR+/ ...

8. fda.gov fda.gov/drugs/resources-information-approved-drugs/palbociclib-ibrance

Palbociclib (IBRANCE) Safety data was evaluated in 444 patients who received palbociclib plus letrozole. Neutropenia was the most frequently reported adverse reaction ...