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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ARM 1 - Letrozole and Palbociclib | Active Comparator | Patients randomized to arm 1 will start standard Letrozole followed by Palbociclib at day 21. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Stereotactic Body Radiation Therapy (SBRT) (50GY in 5 fractions) | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival (PFS) will be measured | Progression free survival (PFS) is defined as the time from the start of study treatment until the disease progression or death. | End of study, up to 36 months. |
| Measure | Description | Time Frame |
|---|---|---|
| Serial levels of Circulating tumor DNA (ctDNA) | Serial levels ctDNA can be an early indication of progression | End of study, up to 36 months. |
| Circulating tumor DNA (ctDNA) levels | Circulating tumor DNA (ctDNA) levels will be measured to determine baseline cancer heterogeneity and its response to treatment |
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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 ā„ 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 ā„ 2000/uL
Absolute neutrophil count (ANC) ā„1500/µL
Platelets ā„100 000/µL
Hemoglobin ā„9.0 g/dL or ā„5.6 mmol/La Renal Creatinine OR Measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ā¤1.5 Ć ULN OR
ā„30 mL/min for the participant with creatinine levels >1.5 Ć institutional ULN Hepatic Total bilirubin ā¤1.5 ĆULN OR direct bilirubin ā¤ULN for participants with total bilirubin levels >1.5 Ć ULN
AST (SGOT) and ALT (SGPT) ā¤2.5 Ć ULN
Coagulation International normalized ratio (INR) OR prothrombin time (PT)
Activated partial thromboplastin time (aPTT) ā¤1.5 Ć ULN unless the participant is receiving anticoagulant therapy if PT or aPTT is within the therapeutic range of intended use of anticoagulants
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fabiana Gregucci, M.D. | Contact | 646-962-3110 | fgr4002@med.cornell.edu |
| Name | Affiliation | Role |
|---|---|---|
| Silvia Formenti, M.D. | Weill Medical College of Cornell University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Weill Cornell Medicine | Recruiting | New York | New York | 10065 | United States |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D016634 | Radiosurgery |
| D000077289 | Letrozole |
| C500026 | palbociclib |
| ID | Term |
|---|---|
| D011878 | Radiotherapy |
| D013812 | Therapeutics |
| D013238 | Stereotaxic Techniques |
| D019635 | Neurosurgical Procedures |
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| Letrozole 2.5Mg Tab | Drug | All patients start standard therapy with oral letrozole (Femara), day 1 of the study. |
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| Palbociclib 125mg | Drug | Patients randomized to arm 2 will start letrozole alone, and add palbociclib on day 21, after completion of I-SBRT. |
|
| End of study, up to 36 months. |
| Objective response rate (ORR) will be assessed. | ORR is defined as the percentage of subjects with either a confirmed complete response (CR) or partial response (PR). | End of study, up to 36 months. |
| Overall survival(OS) will be assessed. | OS is defined as the time from the start of treatment until death. | End of study, up to 36 months. |
| Change in Number of Subjects with Adverse events | Adverse events will be collected from patients based on CTCAE version 5.0. | End of study, up to 36 months. |
| Brooklyn Methodist Hospital - NewYork Presbyterian | Recruiting | New York | New York | 11215 | United States |
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| New York Presbyterian Hospital - Queens | Recruiting | New York | New York | 11355 | United States |
|
| D017437 |
| Skin and Connective Tissue Diseases |
| D013514 |
| Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D009570 | Nitriles |
| D009930 | Organic Chemicals |
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |