A Phase 2 Study of Palliative Radiation in Combination with Pembrolizumab in Subjects with Unresectable Metastatic Stage IV Breast Cancer: Twisted Pink
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Metastatic Breast Cancer
- Sponsor
- University of Louisville
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Primary Outcome Measure
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a phase 2, open-label, single-arm trial designed to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) in combination with pembrolizumab following disease progression after two prior lines of standard therapy in unresectable metastatic stage IV breast cancer
Detailed Description
This study will enroll subjects who are female aged \> 18 years at the time of informed consent with histologically confirmed diagnosis of breast cancer (unresectable or metastatic stage IV breast cancer). Subjects must have measurable disease and be a candidate for palliative stereotactic body radiation therapy (SBRT). Subjects must have Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0, 1, or 2 and adequate hematologic, hepatic, renal, and coagulation function. Subject must also have received two prior lines of FDA-approved therapy. Triple negative patients must have had prior exposure to taxane therapy either in the neoadjuvant/adjuvant or metastatic setting. ER + positive patients must have had prior cyclin dependent kinase (CDK) 4/6 inhibitor therapy. Her2 overexpressed patients must have had prior therapy with trastuzumab and ado-trastuzumab (TDM-1).
Investigators
Elizabeth Riley
Principal Investigator
University of Louisville
Eligibility Criteria
Inclusion Criteria
- •Subject has provided informed consent/assent prior to initiation of any study specific activities/procedures.
- •Female age ≥ 18 years at the time of informed consent.
- •Histologically confirmed diagnosis of breast cancer.
- •Disease stage: unresectable or metastatic stage IV breast cancer.
- •Candidate for palliative SBRT independent from study enrollment
- •Measurable disease, defined as at least 1 visceral or nodal/soft tissue breast cancer lesion that can be accurately and serially measured in at least 1 dimension and for which the longest diameter is ≥ 10 mm as measured by Computer Tomography scan or Magnetic Resonance Imaging. Lymph nodes must measure ≥ 15 mm in their short axis to be considered measurable by Computer Tomography scan or Magnetic Resonance Imaging or Positron Emission Tomography-CT.
- •If subject received major surgery, must have recovered adequately from toxicity and/or complications from the intervention prior to enrollment.
- •Subject must have received two prior lines of therapy and include a taxane in the adjuvant/neoadjuvant or metastatic setting.
- •Triple negative breast cancer patients must have received two lines of chemotherapy in the metastatic setting.
- •ER+/ PR+, ER-/PR+, and ER+/PR- must have received prior Cyclin Dependent Kinase 4/6 Inhibitor in combination with Aromatase Inhibitor or fulvestrant. However, ER+/Her2 overexpressed patients are not required to have received CDK 4/6 inhibitor.
Exclusion Criteria
- •\> 4 Clinically active cerebral metastases. Subjects cerebral metastases may be enrolled, provided that there are less than 4 lesions as these may serve as a site of pallative SBRT
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- •Any active autoimmune disease that in the judgement of the PI or sub-I could be significantly worsened by pembrolizumab
- •Evidence of clinically significant immunosuppression such as the following:
- •diagnosis of immunodeficiency;
- •concurrent opportunistic infection;
- •receiving systemic immunosuppressive therapy (\> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses \> 20 mg/day of prednisone or equivalent Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study.
- •Subject has known sensitivity to any of the products or components to be administered during dosing
- •Known human immunodeficiency virus (HIV) disease.
- •Known acute or chronic hepatitis B or hepatitis C infection.
Outcomes
Primary Outcomes
Primary Outcome Measure
Time Frame: 3.0 years
Overall Response Rate (complete response \[CR\]+partial response \[PR\] by investigator assessment using modified RECIST v1.1) at week 24
Secondary Outcomes
- Secondary Outcome Measures-Best Overall Response Rate(3.0 years)
- Secondary Outcome Measures-Progression-free Survival(3.0 years)
- Secondary Outcome Measures-Incidence of treatment-emergent and treatment-related adverse events(3.0 years)