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

NCT00824733 | Terminated Phase 2 Results DMC

• 2 other identifiers: OSU-08153NCI-2011-03157
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

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

  up to 18 weeks

Secondary Outcomes (2)

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

  up to 18 weeks

• Combination of PF-03512676 and Trastuzumab Induces MIP-1 (Macrophage Inflammatory Protein 1), MCP-1 (Monocyte Chemoattract Protein 1) and RANTES.

  up to 18 weeks

Study Arms (1)

Arm I: Treatment (PF03512676 in combination with Trastuzumab)

EXPERIMENTAL

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; Drug: PF03512676; Other: Correlative Studies

Interventions

Trastuzumab 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.

Also known as: Herceptin

Arm I: Treatment (PF03512676 in combination with Trastuzumab)

PF03512676 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.

Also known as: agatolimod sodium

Arm I: Treatment (PF03512676 in combination with Trastuzumab)

Correlative Studies OTHER

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

Arm I: Treatment (PF03512676 in combination with Trastuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Bhuvaneswari Ramaswamy: lead
• Pfizer: collaborator

Study Sites (1)

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Related Links

• Jamesline

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Trastuzumab; ProMune

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bhuvaneswari Ramaswamy, MD
• Organization: The Ohio State University Comprehensive Cancer Center

Bhuvaneswari.Ramaswamy@osumc.edu

614-293-8858

Study Officials

• Bhuvaneswari Ramaswamy, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 16, 2009
• First Posted: January 19, 2009
• Study Start: February 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: April 1, 2014
• Last Updated: January 14, 2016
• Results First Posted: January 14, 2016

Record last verified: 2015-12

Locations

US (1)