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

Primary Purpose

Metastatic Breast Cancer, Lung Metastases, Liver Metastases

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MEDI6469

About this trial

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Breast Cancer, Metastatic, Lung metastases, Liver metastases, Stereotactic body radiation, anti-OX40 antibody, MEDI6469, Immunotherapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

Portland Providence Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

15 Gy

20 Gy

25 Gy

Arm 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.

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.

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.

Outcomes

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.

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.

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.

Full Information

NCT ID

NCT01862900

First Posted

May 22, 2013

Last Updated

March 19, 2019

Sponsor

Providence Health & Services

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01862900

Brief Title

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

Acronym

OX40 Breast

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

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Completed

Study Start Date

April 27, 2012 (Actual)

Primary Completion Date

May 17, 2016 (Actual)

Study Completion Date

August 15, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Providence Health & Services

Collaborators

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

4. Oversight

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metastatic Breast Cancer, Lung Metastases, Liver Metastases

Keywords

Breast Cancer, Metastatic, Lung metastases, Liver metastases, Stereotactic body radiation, anti-OX40 antibody, MEDI6469, Immunotherapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

14 (Actual)

8. Arms, Groups, and Interventions

Arm Title

15 Gy

Arm Type

Experimental

Arm 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.

Arm Title

20 Gy

Arm Type

Experimental

Arm 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.

Arm Title

25 Gy

Arm Type

Experimental

Arm 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.

Intervention Type

Biological

Intervention Name(s)

MEDI6469

Intervention Description

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

Primary Outcome Measure Information:

Title

Determine the maximum tolerated dose and safety profile of radiation administered in combination with anti-OX40 in patients with metastatic breast cancer.

Description

Time Frame

From Day 1 to Day 36

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

Day 36

Other Pre-specified Outcome Measures:

Title

Determine the influence of anti-OX40 and radiation on circulating CD4+ and CD8+ T cells.

Description

Patients will provide 9 blood samples over 36 days to measure the number of CD4+ and CD8+ T Cells.

Time Frame

Screening to Day 36

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marka R Crittenden, MD, PhD

Organizational Affiliation

Providence Cancer Center, Earle A. Chiles Research Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Brendan Curti, MD

Organizational Affiliation

Providence Cancer Center, Earle A. Chiles Research Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Steven Seung, MD

Organizational Affiliation

Providence Cancer Center, Earle A. Chiles Research Institute

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Alison Conlin, MD

Organizational Affiliation

Providence Cancer Center, Earle A. Chiles Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Portland Providence Medical Center

City

Portland

State/Province

Oregon

ZIP/Postal Code

97213

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Links:

URL

http://oregon.providence.org/patients/programs/providence-cancer-center-clinical-trials/Pages/default.aspx

Description

Providence Cancer Center

Learn more about this trial

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

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