Agatolimod and Trastuzumab in Treating Patients With Locally Advanced or Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT00824733|
Recruitment Status : Terminated (Inaccurate patient accrual for trial)
First Posted : January 19, 2009
Results First Posted : January 14, 2016
Last Update Posted : January 14, 2016
RATIONALE: Biological therapies, such as agatolimod, may stimulate the immune system in different ways and stop tumor cells from growing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving agatolimod together with trastuzumab may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving agatolimod together with trastuzumab works in treating patients with locally advanced or metastatic breast cancer.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Drug: Trastuzumab Drug: PF03512676 Other: Correlative Studies||Phase 2|
- To evaluate the progression-free survival of patients with HER2-overexpressing locally advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and agatolimod sodium.
- To determine if agatolimod sodium augments antibody-mediated cytoxicity (ADCC) against trastuzumab-coated target cells by evaluating the ability of patient immune-effector cells to conduct ADCC and produce interferon gamma.
OUTLINE: This is a multicenter study.
Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on day 1. Patients also receive agatolimod sodium subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Blood samples are collected periodically for correlative laboratory studies. Samples are analyzed for antibody-mediated cytotoxicity (ADCC) by chromium-release assay; IFN-γ production and quantification by flow cytometry and reverse transcriptase-polymerase chain reaction (RT-PCR); and levels of cytokines (IFN-γ and TNF-α) by ELISA.
After completion of study therapy, patients are followed periodically.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Open-label Study of Subcutaneous CPG ODN (PF03512676) in Combination With Trastuzumab in Patients With Metastatic Breast Cancer|
|Study Start Date :||February 2009|
|Actual Primary Completion Date :||February 2013|
|Actual Study Completion Date :||April 2014|
Experimental: Arm I: Treatment (PF03512676 in combination with Trastuzumab)
12 weekly treatments. Week 1-12 patients will receive Trastuzumab 2mg/kg IV(intervenous infusion). Patients who have not been treated wih Trastuzumab within 4 weeks will receive a loading dose of 4 mg/kg on week 1 and PF-03512676-0.16 mg/kg subcutaneous injection.Correlative studies will be drawn on week 1, 2, 6, 12 and 18.
IV at 2 mg/kg over 30 minutes on day 1 of each weekly cycle. Patients who have not received trastuzumab for 4 weeks or more will receive a loading dose of 4 mg/kg over 90 minutes day 1 of the first cycle. The dose of trastuzumab will be based on the patient's actual weight at the start of each 4 week treatment cycle.
Other Name: Herceptin
Patients also receive PF03512676 subcutaneously on days 15 and 22 of course 1 and on days 1, 8, 15, and 22 of all subsequent courses.
Other Name: agatolimod sodium
Other: Correlative Studies
Blood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18.
- PF-03512676 Augments Antibody Mediated Cytoxicity (ADCC)Against Trastuzumab-coated Target Cells in Metastatic HER2 Overexpressing Breast Cancer. [ Time Frame: up to 18 weeks ]
- Progression-free Survival for Patients With Metastatic Breast Cancer That Are Receiving Trastuzumab Plus PF-03512676 [ Time Frame: up to 18 weeks ]Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
- Combination of PF-03512676 and Trastuzumab Induces MIP-1 (Macrophage Inflammatory Protein 1), MCP-1 (Monocyte Chemoattract Protein 1) and RANTES. [ Time Frame: up to 18 weeks ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00824733
|United States, Ohio|
|The Ohio State University Wexner Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Bhuvaneswari Ramaswamy, MD||Ohio State University Comprehensive Cancer Center|