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

Primary Purpose

Breast Cancer

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Trastuzumab

PF03512676

Correlative Studies

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

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

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

Sites / Locations

The Ohio State University Wexner Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I: Treatment (PF03512676 in combination with Trastuzumab)

Arm Description

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.

Outcomes

Primary Outcome Measures

PF-03512676 Augments Antibody Mediated Cytoxicity (ADCC)Against Trastuzumab-coated Target Cells in Metastatic HER2 Overexpressing Breast Cancer.

Secondary Outcome Measures

Progression-free Survival for Patients With Metastatic Breast Cancer That Are Receiving Trastuzumab Plus PF-03512676

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.

Full Information

NCT ID

NCT00824733

First Posted

January 16, 2009

Last Updated

December 9, 2015

Sponsor

Bhuvaneswari Ramaswamy

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT00824733

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Terminated

Why Stopped

Inaccurate patient accrual for trial

Study Start Date

February 2009 (undefined)

Primary Completion Date

February 2013 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Bhuvaneswari Ramaswamy

Collaborators

Pfizer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

6 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm I: Treatment (PF03512676 in combination with Trastuzumab)

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Trastuzumab

Other Intervention Name(s)

Herceptin

Intervention Description

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

Intervention Name(s)

PF03512676

Other Intervention Name(s)

agatolimod sodium

Intervention Description

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

Other

Intervention Name(s)

Correlative Studies

Intervention Description

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

Primary Outcome Measure Information:

Title

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 Measure Information:

Title

Progression-free Survival for Patients With Metastatic Breast Cancer That Are Receiving Trastuzumab Plus PF-03512676

Description

Time Frame

up to 18 weeks

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bhuvaneswari Ramaswamy, MD

Organizational Affiliation

Ohio State University Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

The Ohio State University Wexner Medical Center

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43210

Country

United States

12. IPD Sharing Statement

Links:

URL

http://cancer.osu.edu

Description

Jamesline

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

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