Combined Immunotherapies in Metastatic ER+ Breast Cancer

NCT04563507 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 20-09022641
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 3

Brief Summary

Women with Hormone Receptor (HR)+ Human Epidermal growth factor Receptor (HER)2- metastatic breast cancer are eligible to a randomized trial. Patients receiving standard first line therapy for metastatic HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each metastatic lesion.

Conditions

Breast Cancer

Keywords

metastatic Breast cancer; HR+HER2-; HR + BC; SBRT

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS) will be measured

  Progression free survival (PFS) is defined as the time from the start of study treatment until the disease progression or death.

  End of study, up to 36 months.

Secondary Outcomes (5)

• Serial levels of Circulating tumor DNA (ctDNA)

  End of study, up to 36 months.

• Circulating tumor DNA (ctDNA) levels

  End of study, up to 36 months.

• Objective response rate (ORR) will be assessed.

  End of study, up to 36 months.

• Overall survival(OS) will be assessed.

  End of study, up to 36 months.

• Change in Number of Subjects with Adverse events

  End of study, up to 36 months.

Study Arms (2)

ARM 1 - Letrozole and Palbociclib

ACTIVE COMPARATOR

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

Drug: Letrozole 2.5Mg Tab; Drug: Palbociclib 125mg

ARM 2 - Letrozole and Palbociclib + I-SBRT

ACTIVE COMPARATOR

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.

Radiation: Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions); Drug: Letrozole 2.5Mg Tab; Drug: Palbociclib 125mg

Interventions

Letrozole 2.5Mg Tab DRUG

All patients start standard therapy with oral letrozole (Femara), day 1 of the study.

ARM 1 - Letrozole and Palbociclib; ARM 2 - Letrozole and Palbociclib + I-SBRT

Palbociclib 125mg DRUG

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT.

ARM 1 - Letrozole and Palbociclib; ARM 2 - Letrozole and Palbociclib + I-SBRT

Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions) RADIATION

Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. They will undergo tumor Immunogenic-SBRT(I-SBRT) days 1-12 (+/-2 days, to enable inclusion of holidays). During the week preceding day 1, they will undergo simulation and planning for radiotherapy. Each oligometastatic lesion will be treated with I-SBRT every 48 hours. 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

ARM 2 - Letrozole and Palbociclib + I-SBRT

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female ≥ 18 years of age pre and post-menopausal
• Metastatic disease (≤ 5 sites of measurable disease by RECIST)
• Eligible for treatment with CDK4/6 + aromatase inhibitors
• Premenopausal status is defined as either:
• Patient had last menstrual period within the last 12 months, OR
• If on tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, OR
• In case of therapy-induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range.
• Patients who have undergone bilateral oophorectomy are eligible.
• Post-menopausal status defined as either 1) at least 2 years without menstrual period or 2) patients older than 50 with serological evidence of post-menopausal status or 3) hysterectomized patients of any age with FSH confirmation of post-menopausal status.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Biopsy proven diagnosis of HR+HER2- metastatic breast cancer. ER expression is \>10%
• Patient needs to be able to understand and demonstrate a willingness to sign a written informed consent document
• Hematological WBC ≥ 2000/uL
• Absolute neutrophil count (ANC) ≥1500/µL
• Platelets ≥100 000/µL

You may not qualify if:

• Active connective tissue disorders, such as lupus or scleroderma requiring flare therapy
• Current use of systemic chemotherapy, endocrine therapy or HER2-neu targeted therapy
• Any lesion \>5 cm in greatest diameter.
• Inability to obtain histologic proof of metastatic breast cancer
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy (second primary) that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has an active infection requiring systemic therapy. Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Patients with uncontrolled brain metastases

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (3)

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

Brooklyn Methodist Hospital - NewYork Presbyterian

New York, New York, 11215, United States

RECRUITING

New York Presbyterian Hospital - Queens

New York, New York, 11355, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Radiosurgery; Letrozole; palbociclib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Silvia Formenti, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fabiana Gregucci, M.D.

CONTACT

646-962-3110; fgr4002@med.cornell.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2020
• First Posted: September 24, 2020
• Study Start: November 12, 2020
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2028
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)