Combined Immunotherapies in Metastatic ER+ Breast Cancer

NCT ID: NCT04563507

Last Updated: 2025-12-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-12
• Study Completion Date: 2028-10-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARM 1 - Letrozole and Palbociclib

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

Group Type: ACTIVE_COMPARATOR

Letrozole 2.5Mg Tab

Intervention Type: DRUG

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

Palbociclib 125mg

Intervention Type: DRUG

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

ARM 2 - Letrozole and Palbociclib + I-SBRT

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 Type: ACTIVE_COMPARATOR

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

Intervention Type: 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

Letrozole 2.5Mg Tab

Intervention Type: DRUG

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

Palbociclib 125mg

Intervention Type: DRUG

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

Interventions

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

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

Intervention Type: RADIATION

Letrozole 2.5Mg Tab

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

Intervention Type: DRUG

Palbociclib 125mg

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR

≥30 mL/min for the participant with creatinine levels >1.5 × institutional ULN Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN

• AST (SGOT) and ALT (SGPT) ≤2.5 × ULN
• Coagulation International normalized ratio (INR) OR prothrombin time (PT)
• Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless the participant is receiving anticoagulant therapy if PT or aPTT is within the therapeutic range of intended use of anticoagulants

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Silvia Formenti, M.D.

Role: PRINCIPAL_INVESTIGATOR

Weill Medical College of Cornell University

Locations

Weill Cornell Medicine

New York, New York, United States

Site Status: RECRUITING

Brooklyn Methodist Hospital - NewYork Presbyterian

New York, New York, United States

Site Status: RECRUITING

New York Presbyterian Hospital - Queens

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Fabiana Gregucci, M.D.

Role: CONTACT

fgr4002@med.cornell.edu

646-962-3110

Facility Contacts

Fabiana Gregucci, M.D.

Role: primary

fgr4002@med.cornell.edu

6469623110

Izael Niño, M.S.

Role: primary

izn4001@med.cornell.edu

929 470 9426

Hina Ali, M.D.

Role: primary

hia4002@med.cornell.edu

Other Identifiers

20-09022641

Identifier Type: -

Identifier Source: org_study_id