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

Sponsor

Providence Health & Services (Other)

Overall Status

Completed

CT.gov ID

NCT01862900

Collaborator

Robert W. Franz Cancer Center (Other), Providence Cancer Center, Earle A. Chiles Research Institute (Other), MedImmune LLC (Industry)

Enrollment

Location

Arms

75.6

Actual Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Breast Cancer Lung Metastases Liver Metastases	Biological: MEDI6469	Phase 1

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

14 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Apr 27, 2012

Actual Primary Completion Date :

May 17, 2016

Actual Study Completion Date :

Aug 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 15 Gy 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 Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5
Experimental: 20 Gy 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 Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5
Experimental: 25 Gy 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 Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5

Arm

Intervention/Treatment

Experimental: 15 Gy

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

Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5

Experimental: 20 Gy

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

Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5

Experimental: 25 Gy

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

Patients receive 3 doses of MEDI6469; one on Days 1, 3, and 5

Outcome Measures

Primary Outcome Measures

Determine the maximum tolerated dose and safety profile of radiation administered in combination with anti-OX40 in patients with metastatic breast cancer. [From Day 1 to Day 36]
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.

Secondary Outcome Measures

Estimate the response rate of combined modality treatment in both irradiated and non-irradiated tumors. [Day 36]
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.

Other Outcome Measures

Determine the influence of anti-OX40 and radiation on circulating CD4+ and CD8+ T cells. [Screening to Day 36]
Patients will provide 9 blood samples over 36 days to measure the number of CD4+ and CD8+ T Cells.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Portland Providence Medical Center	Portland	Oregon	United States	97213

Sponsors and Collaborators

Providence Health & Services
Robert W. Franz Cancer Center
Providence Cancer Center, Earle A. Chiles Research Institute
MedImmune LLC

Investigators

Principal Investigator: Marka R Crittenden, MD, PhD, Providence Cancer Center, Earle A. Chiles Research Institute
Principal Investigator: Brendan Curti, MD, Providence Cancer Center, Earle A. Chiles Research Institute
Principal Investigator: Steven Seung, MD, Providence Cancer Center, Earle A. Chiles Research Institute
Principal Investigator: Alison Conlin, MD, Providence Cancer Center, Earle A. Chiles Research Institute