Description:
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.
Title
- Brief Title: Combined Immunotherapies in Metastatic ER+ Breast Cancer
- Official Title: CIMER: Combined Immunotherapies in Metastatic ER+ Breast Cancer
Clinical Trial IDs
- ORG STUDY ID:
20-09022641
- NCT ID:
NCT04563507
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Letrozole 2.5Mg Tab | | ARM 1 - Letrozole and Palbociclib |
Palbociclib 125mg | | ARM 1 - Letrozole and Palbociclib |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
ARM 1 - Letrozole and Palbociclib | Active Comparator | Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21. | - Letrozole 2.5Mg Tab
- 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. | - Letrozole 2.5Mg Tab
- Palbociclib 125mg
|
Eligibility Criteria
Inclusion Criteria:
- Female ≥ 18 years of age pre and post-menopausal
- Metastatic disease (≤ 5 sites of measurable disease)
- 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
- Male breast cancer patients
- 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
Maximum Eligible Age: | 90 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | Female |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression free survival (PFS) will be measured |
Time Frame: | End of study, up to 36 months. |
Safety Issue: | |
Description: | Progression free survival (PFS) is defined as the time from the start of study treatment until the disease progression or death. |
Secondary Outcome Measures
Measure: | Serial levels of Circulating tumor DNA (ctDNA) |
Time Frame: | End of study, up to 36 months. |
Safety Issue: | |
Description: | Serial levels ctDNA can be an early indication of progression |
Measure: | Circulating tumor DNA (ctDNA) levels |
Time Frame: | End of study, up to 36 months. |
Safety Issue: | |
Description: | Circulating tumor DNA (ctDNA) levels will be measured to determine baseline cancer heterogeneity and its response to treatment |
Measure: | Objective response rate (ORR) will be assessed. |
Time Frame: | End of study, up to 36 months. |
Safety Issue: | |
Description: | ORR is defined as the percentage of subjects with either a confirmed complete response (CR) or partial response (PR). |
Measure: | Overall survival(OS) will be assessed. |
Time Frame: | End of study, up to 36 months. |
Safety Issue: | |
Description: | OS is defined as the time from the start of treatment until death. |
Measure: | Change in Number of Subjects with Adverse events |
Time Frame: | End of study, up to 36 months. |
Safety Issue: | |
Description: | Adverse events will be collected from patients based on CTCAE version 5.0. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Weill Medical College of Cornell University |
Trial Keywords
- metastatic Breast cancer
- HR+HER2-
- HR + BC
- SBRT
Last Updated
July 1, 2021