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A Phase II Open-label Study of Subcutaneous CPG ODN (PF03512676) in Combination With Trastuzumab in Patients With Metastatic Breast Cancer

Phase 2
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Phase II Open-label Study of Subcutaneous CPG ODN (PF03512676) in Combination With Trastuzumab in Patients With Metastatic Breast Cancer



- 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.

Inclusion Criteria


- Histologically or cytologically confirmed breast cancer

- Locally advanced or metastatic disease

- HER2-overexpressing tumor, defined as 3+ overexpression by IHC and/or HER2 amplified

- 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

- 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

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Determine if PF-03512676 augments antibody mediated cytoxicity (ADCC)against trastuzumab-coated target cells in metastatic HER2 overexpressing breast cancer.

Outcome Time Frame:

up to 18 weeks

Safety Issue:


Principal Investigator

Bhuvaneswari Ramaswamy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University


United States: Food and Drug Administration

Study ID:




Start Date:

February 2009

Completion Date:

Related Keywords:

  • Breast Cancer
  • 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
  • Breast Neoplasms



Ohio State UniversityColumbus, Ohio  43210