Stereotactic Body Radiation and Monoclonal Antibody to OX40 (MEDI6469) in Breast Cancer Patients With Metastatic Lesions

Study Overview
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Brief Summary
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This study will test the investigational antibody, MEDI6469 (anti-OX40), in combination with stereotactic body radiation in breast cancer patients that have liver or lung metastases and have received systemic therapy and have progressive disease. The investigators hypothesize that SBRT directed at metastatic breast cancer lesions will result in a systemic anti-tumor immune system response. This amplified and directed immune response could result in anti-tumor responses.

Detailed Description
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Patients will receive one of three different doses of SBRT depending on which cohort they are in. The doses are: Cohort 1: 15 Gy (central tumors 10 Gy); Cohort 2: 20 Gy (central tumors 15 Gy); Cohort 3: 20 Gy x 2 (central tumors 15 Gy x 2). In addition, all patients will receive three doses of MEDI6469. MEDI6469 is administered at 0.4 mg/kg IV over 60 minutes using in-line filter on Days 1, 3, and 5.

Official Title
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Phase I/II Study of Stereotactic Body Radiation Therapy to Metastatic Lesions in the Liver or Lung in Combination With Monoclonal Antibody to OX40 (MEDI6469) in Patients With Progressive Metastatic Breast Cancer After Systemic Therapy.

Conditions
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Metastatic Breast Cancer, Lung Metastases, Liver Metastases

Intervention / Treatment
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* Biological: MEDI6469


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed breast cancer with clinical evidence of stage 4 disease Measurable disease and at least one lesion in either liver or lung that is amenable to stereotactic body radiation One site of disease that will not receive radiation Patients with hormone receptor positive breast cancer must have received prior anti-hormonal therapy for metastatic disease and have progressed and patients with hormone receptor negative breast cancer must have received at least one prior chemotherapy regimen and progressed. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2. Women of childbearing potential must have a negative pregnancy test on the day treatment starts and must avoid becoming pregnant while on treatment. Men must avoid fathering a child while on treatment. Patients must have blood test results within pre-specified range No active bleeding No clinical coagulopathy (INR <1.5, PT <16 seconds, PTT < 38 seconds) within 28 days Anticipated lifespan greater than 12 weeks Exclusion Criteria: Active infection requiring systemic antibiotics. Active autoimmune disease as defined by the autoimmune disease assessment tool. Previous treatment with mouse monoclonal antibodies At least 28 days since prior chemotherapy or monoclonal antibody therapy (trastuzumab or bevacizumab). Patients who have been on hormonal therapy can continue on therapy at the discretion of the investigator. Bisphosphonate therapy is acceptable during study participation. Diagnosis of a solid tumor malignancy (excluding non-melanoma skin cancer) within 3 years of enrollment. Need for chronic maintenance oral steroids. Active brain metastatic disease. Treated brain metastases with surgery, gamma-knife radiosurgery or radiation and stable for at least 4 weeks and off steroids are eligible. No metastatic site amenable to SBRT Pregnant or lactating women, as treatment involves risks to the embryo or fetus. Other medical or psychiatric conditions that in the opinion of the Principal Investigator would preclude safe participation in protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15 Gy<br>Patients receive a radiation dose of 15 Gy to their liver or lung metastases. Patients receive a dose of MEDI6469 following radiation and on Days 3, and 5. | Biological: MEDI6469<br>* Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5<br>|
| Experimental: 20 Gy<br>Patients receive a radiation dose of 20 Gy to their liver or lung metastases. Patients receive a dose of MEDI6469 following radiation and on Days 3, and 5. | Biological: MEDI6469<br>* Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5<br>|
| Experimental: 25 Gy<br>Patients receive a radiation dose of 25 Gy to their liver or lung metastases. Patients receive a dose of MEDI6469 following radiation and on Days 3, and 5. | Biological: MEDI6469<br>* Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose and safety profile of radiation administered in combination with anti-OX40 in patients with metastatic breast cancer. | A dose limiting toxicity (DLT) is defined as any greater than or equal to grade 3 non-hematologic toxicity (except hypothyroidism or vitiligo) that in the opinion of the investigator is considered at least possibly related to treatment. Grade 3 or 4 hematologic toxicities that take longer than 10 days to resolve will be considered DLTs. Patients will have 8 clinic visits over 36 days to identify toxicities. | From Day 1 to Day 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate the response rate of combined modality treatment in both irradiated and non-irradiated tumors. | Patients will have CT scans for tumor measurements at Day 36. Patients achieving a radiographic response, or are stable, will be followed monthly with physical exam and laboratory studies with CT (or other imaging as deemed appropriate) scans obtained every 3 months (± 2 weeks) for up to 24 months and then ever 6 months (± 2 weeks) for up to 4 years. | Day 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver metastases, Stereotactic body radiation, anti-OX40 antibody, Immunotherapy, Breast Cancer, Metastatic, Lung metastases, MEDI6469