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Initiating a new study with revised Statistics.
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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. |
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| 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. |
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| 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 |
|---|---|---|
| Number of subjects achieving 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. |
| Number of Subjects achieving Progression free survival (PFS) | 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. |
| Number of subjects achieving 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. |
| 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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Inclusion Criteria:
Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Silvia Formenti, M.D. | Weill Medical College of Cornell University | Principal Investigator |
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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. |
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| End of study, up to 36 months. |
| 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 |