Clinical trial NCT01862900: Stereotactic Body Radiation and Monoclonal Antibody to OX40 (MEDI6469) in Breast Cancer Patients With Metastatic Lesions
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metastatic Breast Cancer
Lung Metastases
Liver Metastases
Keywords: Breast Cancer
Metastatic
Lung metastases
Liver metastases
Stereotactic body radiation
anti-OX40 antibody
MEDI6469
Immunotherapy
Lead sponsor: Providence Health & Services
Sponsor class: OTHER
Collaborators: name: Robert W. Franz Cancer Center
name: Providence Cancer Center, Earle A. Chiles Research Institute
name: MedImmune LLC
First posted: 2013-05-27
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Determine the maximum tolerated dose and safety profile of radiation administered in combination with anti-OX40 in patients with metastatic breast cancer.
timeFrame: From Day 1 to Day 36
Secondary outcomes:
measure: Estimate the response rate of combined modality treatment in both irradiated and non-irradiated tumors.
timeFrame: Day 36
Other outcomes:
measure: Determine the influence of anti-OX40 and radiation on circulating CD4+ and CD8+ T cells.
timeFrame: Screening to Day 36
Locations:
city: Portland
country: United States
facility: Portland Providence Medical Center
state: Oregon
Study officials:
affiliation: Providence Cancer Center, Earle A. Chiles Research Institute
name: Marka R Crittenden, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Cancer Center, Earle A. Chiles Research Institute
name: Brendan Curti, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Cancer Center, Earle A. Chiles Research Institute
name: Steven Seung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Providence Cancer Center, Earle A. Chiles Research Institute
name: Alison Conlin, MD
role: PRINCIPAL_INVESTIGATOR
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