We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Agatolimod and Trastuzumab in Treating Patients With Locally Advanced or Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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
Information provided by (Responsible Party):
Bhuvaneswari Ramaswamy, Ohio State University Comprehensive Cancer Center

Brief Summary:

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

Detailed Description:



  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Trastuzumab

Arm Intervention/treatment
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.
Drug: Trastuzumab
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

Drug: PF03512676
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.

Primary Outcome Measures :
  1. PF-03512676 Augments Antibody Mediated Cytoxicity (ADCC)Against Trastuzumab-coated Target Cells in Metastatic HER2 Overexpressing Breast Cancer. [ Time Frame: up to 18 weeks ]

Secondary Outcome Measures :
  1. 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

  2. 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 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically or cytologically confirmed breast cancer

    • Locally advanced or metastatic disease
  • HER2-overexpressing tumor, defined as 3+ overexpression by IHC and/or HER2 amplified by FISH
  • Non-measurable disease allowed
  • Achieved partial response, complete response, or stable disease (i.e., no disease progression for ≥ 12 weeks) while on trastuzumab (Herceptin®) and chemotherapy, hormonal therapy alone, or trastuzumab alone

    • Last dose of trastuzumab must have been administered within the past 16 weeks
  • No unstable brain metastases

    • Patients with brain metastases are eligible provided they have been stable for ≥ 1 month after surgery or radiotherapy/radiosurgery AND off corticosteroids and anticonvulsants for ≥ 4 weeks
  • Hormone receptor status unspecified


  • ECOG(Eastern Cooperative Oncology Group)performance status (PS) 0-2 (Karnofsky PS 70-100%)
  • Absolute neutrophil count ≥ 1,500/mm³
  • Hemoglobin > 8 g/dL (transfusion/epoetin alfa allowed)
  • Platelet count ≥ 100,000/mm³
  • Total bilirubin < 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN (≤ 5.0 times ULN if known liver metastases)
  • Creatinine < 2 mg/mL
  • Ejection fraction ≥ 50% by echocardiogram or MUGA
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception before, during, and for ≥ 3 months after completion of study treatment
  • No ongoing or active infection requiring oral or IV antibiotics
  • No known autoimmune disorders or antibody-mediated disorders
  • No known HIV positivity
  • No known history of hepatitis B or C (active and/or previously treated)
  • No other malignancies within the past 5 years except nonmelanoma skin cancer or cervical cancer in situ
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs


  • See Disease Characteristics
  • More than 12 weeks since prior chloroquine
  • More than 4 weeks since prior growth factors
  • More than 4 weeks since prior systemic corticosteroids
  • More than 4 weeks since prior chemotherapy, radiotherapy, or monoclonal antibody therapy (except trastuzumab)
  • No prior agatolimod sodium
  • No prior allogeneic stem cell transplantation
  • No prior continuous treatment with single-agent trastuzumab for > 6 months
  • No more than 3 prior chemotherapy regimens for metastatic breast cancer
  • Any number of prior hormonal therapies allowed
  • No other concurrent investigational agents or monoclonal antibodies
  • No other concurrent anticancer agents or therapies
  • Concurrent bisphosphonates for skeletal metastasis allowed

Information from the National Library of Medicine

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

Layout table for location information
United States, Ohio
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Bhuvaneswari Ramaswamy
Layout table for investigator information
Principal Investigator: Bhuvaneswari Ramaswamy, MD Ohio State University Comprehensive Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Bhuvaneswari Ramaswamy, Principal Investigator, Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00824733    
Other Study ID Numbers: OSU-08153
NCI-2011-03157 ( Registry Identifier: Clinical Trial Reporting Program (CTRP) )
First Posted: January 19, 2009    Key Record Dates
Results First Posted: January 14, 2016
Last Update Posted: January 14, 2016
Last Verified: December 2015
Keywords provided by Bhuvaneswari Ramaswamy, Ohio State University Comprehensive Cancer Center:
recurrent breast cancer
stage IV breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
HER2-positive breast cancer
male breast cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents