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

Providence Health & Services

Status and phase: Completed; Phase 1

Conditions: Liver Metastases; Metastatic Breast Cancer; Lung Metastases

Treatments: Biological: MEDI6469

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01862900

12-017A

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 14 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

14 participants in 3 patient groups

15 Gy

Experimental group

Description:

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.

Treatment:

Biological: MEDI6469

20 Gy

Experimental group

Description:

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.

Treatment:

Biological: MEDI6469

25 Gy

Experimental group

Description:

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.

Treatment:

Biological: MEDI6469