Combining immunotherapies for metastatic ER+ breast cancer

CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer

This study is testing if adding a type of radiation therapy to standard treatment can help women with metastatic hormone receptor-positive breast cancer feel better and live longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 102 (estimated)
• Ages: 18 Years to 90 Years
• Sex: Female
• Sponsor: Weill Medical College of Cornell University (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, Radiation
• Locations: 3 sites (New York, New York and 2 other locations)
• Trial ID: NCT04563507 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining Stereotactic Body Radiation Therapy (SBRT) with standard first-line therapy (letrozole and palbociclib) in women with metastatic hormone receptor-positive (HR+) and HER2-negative breast cancer. Participants will be randomly assigned to receive either the standard treatment alone or the combination treatment. The goal is to evaluate whether adding SBRT to the existing therapy improves outcomes for patients with metastatic breast cancer.

Who should consider this trial

Good fit: Ideal candidates include women aged 18 and older with newly diagnosed or previously treated metastatic HR+ HER2- breast cancer who have shown progression after one line of endocrine therapy.

Not a fit: Patients with non-metastatic breast cancer or those who have not progressed after initial endocrine therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could enhance treatment efficacy and improve survival rates for patients with metastatic HR+ breast cancer.

How similar studies have performed: Other studies have shown promise in combining radiation therapy with systemic treatments for breast cancer, suggesting potential for success in this approach.

Eligibility criteria

Newly diagnosed advanced/metastatic breast cancer at diagnosis that progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor) (AND/OR) Previously diagnosed and treated metastatic BC, for the first time being offered CDK4/6 inhibition with endocrine therapy ( can have progressed after endocrine therapy before) Male Breast cancer patients are eligible to participate on the trial.

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

Where this trial is running

New York, New York and 2 other locations

• Weill Cornell Medicine — New York, New York, United States (Recruiting)
• Brooklyn Methodist Hospital - NewYork Presbyterian — New York, New York, United States (Recruiting)
• New York Presbyterian Hospital - Queens — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: Silvia Formenti, M.D. — Weill Medical College of Cornell University
• Study coordinator: Fabiana Gregucci, M.D.

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