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

NCT ID: NCT00824733

Last Updated: 2016-01-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-02-28
• Study Completion Date: 2014-04-30

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.

Detailed Description

OBJECTIVES:

Primary

• To evaluate the progression-free survival of patients with HER2-overexpressing locally advanced or metastatic breast cancer treated with trastuzumab (Herceptin®) and agatolimod sodium.

Secondary

• 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.

Conditions

Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Trastuzumab

Intervention Type: DRUG

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.

PF03512676

Intervention Type: DRUG

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.

Correlative Studies

Intervention Type: OTHER

Blood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Correlative Studies

Blood for performing the correlative studies will be drawn on week 1, 2, 6, 12 and 18.

Intervention Type: OTHER

Other Intervention Names

Herceptin; agatolimod sodium

Eligibility Criteria

Inclusion Criteria

• Hormone receptor status unspecified

PATIENT CHARACTERISTICS:

• 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

PRIOR CONCURRENT THERAPY:

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Bhuvaneswari Ramaswamy

OTHER

Sponsor Role: lead

Responsible Party

Bhuvaneswari Ramaswamy

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Bhuvaneswari Ramaswamy, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Countries

United States

Related Links

http://cancer.osu.edu

Jamesline

Other Identifiers

NCI-2011-03157

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-08153

Identifier Type: -

Identifier Source: org_study_id