Combined Immunotherapies in Metastatic ER+ Breast Cancer

Weill Cornell Medicine (WCM)

Status and phase: Enrolling; Phase 2

Conditions: Breast Cancer

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

Study type: Interventional

Funder types: Other

Identifiers

NCT04563507

20-09022641

Details and patient eligibility

About

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.

Enrollment: 102 estimated patients

Sex: Female

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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102 participants in 2 patient groups

ARM 1 - Letrozole and Palbociclib

Active Comparator group

Description:

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

Treatment:

Drug: Letrozole 2.5Mg Tab

Drug: Palbociclib 125mg

ARM 2 - Letrozole and Palbociclib + I-SBRT

Active Comparator group

Description:

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.

Treatment:

Drug: Letrozole 2.5Mg Tab

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

Drug: Palbociclib 125mg