Stereotactic Radiation and OX40 in Patients With Breast Cancer Metastatic to the Liver or Lung (OX40 SBRT)

• Estimate the response rate of combined modality treatment in both irradiated and non-irradiated tumors. [ Time Frame: Up to four years, depending on patient response to treatment ] [ Designated as safety issue: No ]
  Follow up after day 36 (the completion of the study) will be dictated by the clinical response. 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 will obtained every 3 months for up to 24 months and then ever 6 months for up to 4 years.
• Determine the influence of anti-OX40 and radiation on circulating CD4+ and CD8+ T cells. [ Time Frame: Depending on patient response, up to 4 years. ] [ Designated as safety issue: No ]
  Blood samples will be collected from peripheral access for immune monitoring at Days, 2, 3, 5, 8, 15, 29, and 36. During the follow-up period, every 3 months for up to 24 months and then ever 6 months for up to 4 years.

This is a study for patients with progressive metastatic breast cancer following systemic therapy who have lesions on the lungs or liver. The study is designed to find the maximum dose of radiation that can be given with anti-OX40.

This is a phase I/II study to determine the maximum tolerated dose of stereotactic body radiation given with anti-OX40. Three different dose levels of radiation will be tested. All patients will receive three doses of anti-OX40 given over a 60 minute IV infusion. Up to 18 patients will be treated during the dose escalation phase, and an additional 20 at the maximum tolerated dose.

• Breast Cancer, Metastatic
• Malignant Neoplasm of Breast TNM Stage M1

• Radiation: 15 Gy Radiation plus anti-OX40
  Patients receive a single fraction of radiation on Day 1 (15Gy) and receive .4mg/kg of anti-OX40 on Days 1, 3, and 5.
• Drug: anti-OX40
  anti-OX40 given at .4mg/kg on Days 1, 3, and 5
• Radiation: 20 Gy radiation and anti-OX40
  Patients receive a single fraction of radiation on Day 1 (20 Gy) and receive .4mg/kg of anti-OX40 on Days 1, 3, and 5.
• Radiation: 25 Gy radiation and anti-OX40
  Patients receive a single fraction of radiation on Day 1 (25 Gy) and receive .4mg/kg of anti-OX40 on Days 1, 3, and 5.

• Experimental: Cohort 1
  Cohort 1 will receive a single fraction of stereotactic body radiation at a level of 15 Gy. Patient will receive doses of anti-OX40 on Days 1, 3, and 5.
  Interventions:

  • Radiation: 15 Gy Radiation plus anti-OX40
  • Drug: anti-OX40
• Experimental: Cohort 2
  Cohort 2 will receive a single fraction of stereotactic body radiation at a level of 20 Gy. Patient will receive doses of anti-OX40 on Days 1, 3, and 5.
  Interventions:

  • Drug: anti-OX40
  • Radiation: 20 Gy radiation and anti-OX40
• Experimental: Cohort 3
  Cohort 3 will receive a single fraction of stereotactic body radiation at a level of 25 Gy. Patient will receive doses of anti-OX40 on Days 1, 3, and 5.
  Interventions:

  • Drug: anti-OX40
  • Radiation: 25 Gy radiation and anti-OX40

Inclusion Criteria:

• Stage 4 histologically confirmed breast cancer
• At least 1 lesion in the liver or lung amenable to SBRT
• 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.
• ECOG performance status of 0, 1, or 2
• Anticipated life span greater than 12 weeks

Exclusion Criteria:

• Active infection
• Active autoimmune disease
• Previous treatment with mouse monoclonal antibodies
• Brain metastatic disease