CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer
Phase 2
Withdrawn
- Conditions
- Breast Cancer
- Interventions
- Radiation: Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions)
- Registration Number
- NCT04220476
- Lead Sponsor
- Weill Medical College of Cornell University
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
Inclusion Criteria
- Female ≥ 18 years of age pre and post-menopausal
- Oligometastatic disease (≤ 5 sites of disease)
- 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 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 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 participant is receiving anticoagulant therapy if PT or aPTT is within 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
- Male breast cancer patients
- Any lesion >5 cm in greatest diameter.
- Inability to obtain histologic proof of metastatic breast cancer
- Has received previous endocrine or chemotherapy for 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ARM 1 - Letrozole and Palbociclib Palbociclib 125mg Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21. ARM 2 - Letrozole and Palbociclib + I-SBRT Letrozole 2.5Mg Tab 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. ARM 2 - Letrozole and Palbociclib + I-SBRT Palbociclib 125mg 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. ARM 1 - Letrozole and Palbociclib Letrozole 2.5Mg Tab Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21. ARM 2 - Letrozole and Palbociclib + I-SBRT 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. 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.
- Primary Outcome Measures
Name Time Method Number of subjects achieving Overall survival(OS) will be assessed. End of study, up to 36 months. OS is defined as the time from the start of treatment until death.
Number of subjects achieving Objective response rate (ORR) will be assessed. End of study, up to 36 months. ORR is defined as the percentage of subjects with either a confirmed complete response (CR) or partial response (PR).
Number of Subjects achieving Progression free survival (PFS) End of study, up to 36 months. Progression free survival (PFS) is defined as the time from the start of study treatment until the disease progression or death.
- Secondary Outcome Measures
Name Time Method Serial levels of Circulating tumor DNA (ctDNA) End of study, up to 36 months. serial levels ctDNA can be an early indication of progression
Circulating tumor DNA (ctDNA) levels End of study, up to 36 months. Circulating tumor DNA (ctDNA) levels will be measured to determine baseline cancer heterogeneity and its response to treatment