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

NCT01862900 | Completed Phase 1

• 1 other identifier: 12-017A
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Breast Cancer; Lung Metastases; Liver Metastases

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  From Day 1 to Day 36

Secondary Outcomes (1)

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

  Day 36

Other Outcomes (1)

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

  Screening to Day 36

Study Arms (3)

15 Gy

EXPERIMENTAL

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

20 Gy

EXPERIMENTAL

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

25 Gy

EXPERIMENTAL

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

Interventions

MEDI6469 BIOLOGICAL

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

15 Gy; 20 Gy; 25 Gy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Portland Providence Medical Center

Portland, Oregon, 97213, United States

Location

Related Links

• Providence Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2013
• First Posted: May 27, 2013
• Study Start: April 27, 2012
• Primary Completion: May 17, 2016
• Study Completion: August 15, 2018
• Last Updated: March 21, 2019

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)