Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

NCT ID: NCT00791037

Last Updated: 2017-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2014-12-31

Brief Summary

This phase I/II trial is studying the side effects of escalating doses of adoptive T cell therapy in treating patients with stage IV breast cancer. Vaccines are given to patient prior the expansion of a person's white blood cells may help the body build an effective immune response to kill tumor cells that overexpress human epidermal growth factor receptor 2 (HER2)

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the safety of infusing escalating doses of HER2 specific T cells into patients with advanced HER2+ breast cancer using ex vivo expanded autologous T cells.

SECONDARY OBJECTIVES:

I. To investigate to what extent HER2 specific T cell immunity can be boosted or generated in individuals after infusion of HER2 specific T cells.

II. To evaluate how long T cell immune augmentation persists in vivo after adoptive transfer of HER2 specific T cells and subsequent booster immunizations.

III. To determine the development of cluster of differentiation (CD)4+ and CD8+ epitope spreading after adoptive transfer of HER2 specific T cells.

TERTIARY OBJECTIVES:

I. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with advanced HER2+ breast cancer.

II. To determine whether indium-labeled HER-2 specific T-cells traffic to sites of metastatic disease once adoptively transferred using SPECT or SPECT-CT imaging.

III. To assess whether adoptively transferred HER-2 specific T-cells induce acute inflammation at metastatic sites of disease by assessing the development of tumor inflammation after the second or third infusion of cells using PET-CT imaging.

OUTLINE: This is a phase I/II, dose-escalation study of ex vivo-expanded HER2-specific autologous T cells.

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) intradermally (ID) on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.

Patients receive cyclophosphamide intravenously (IV) once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three treatments. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.

While on the study, patients may continue their standard-of-care (non-research) treatment with trastuzumab and/or lapatinib IV weekly or every 3 weeks, except for 7 days before the cyclophosphamide dose, treatment 1 and treatment 2 and at least 7 days after receiving the second T cell vaccine. (Trastuzumab and lapatinib are not required or provided in this study).

Before the third T cell treatment of HER2 specific T-cells we will label a small sample of the patient's T-cells with indium-111. Prior to the final infusion of T-cells, patients will have FDG PET-CT performed. This scan will be repeated 48 hours after T-cell infusion. In addition, patients would then undergo SPECT or SPECT-CT imaging at 4, 24, 48, and 72 hours (+/- 3 hours) after labeled cells have been infused.

After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for the following year, and then twice a year thereafter. This consists of blood collection and contact with patients physician.

Conditions

HER2-positive Breast Cancer; Male Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Study Design

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

Study Groups

Treatment (vaccine therapy)

Patients receive HER2/neu peptide vaccine admixed with sargramostim (GM-CSF) ID on days 1, 8, and 15. Beginning 2 weeks later, patients undergo leukapheresis to isolate and collect peripheral blood mononuclear cells for T-cell expansion.

Patients receive cyclophosphamide IV once on day -1 and autologous ex vivo-expanded HER2-specific T cell IV over 30 minutes on day 1. Treatment repeats every 7-10 days for up to three immunizations. Patients receive a booster HER2/neu peptide vaccine 1 month after the final T-cell infusion, followed by 2 additional booster vaccines at 2-month intervals.

Group Type: EXPERIMENTAL

HER-2/neu peptide vaccine

Intervention Type: BIOLOGICAL

Given ID

leukapheresis

Intervention Type: PROCEDURE

Undergo leukapheresis

ex vivo-expanded HER2-specific T cells

Intervention Type: BIOLOGICAL

Given IV

cyclophosphamide

Intervention Type: DRUG

Given IV

sargramostim

Intervention Type: BIOLOGICAL

Given ID

laboratory biomarker analysis

Intervention Type: OTHER

Correlative study

Interventions

HER-2/neu peptide vaccine

Given ID

Intervention Type: BIOLOGICAL

leukapheresis

Undergo leukapheresis

Intervention Type: PROCEDURE

ex vivo-expanded HER2-specific T cells

Given IV

Intervention Type: BIOLOGICAL

cyclophosphamide

Given IV

Intervention Type: DRUG

sargramostim

Given ID

Intervention Type: BIOLOGICAL

laboratory biomarker analysis

Correlative study

Intervention Type: OTHER

Other Intervention Names

HER-2; CPM; CTX; Cytoxan; Endoxan; Endoxana; GM-CSF; Leukine; Prokine

Eligibility Criteria

Inclusion Criteria

• Patients with HER2+ Stage IV breast cancer that have been maximally treated and not achieved a complete remission
• Patients must have stable or slowly progressive disease state, measurable disease as:

• Extraskeletal disease that can be accurately measured >= 10 mm by standard imaging techniques that can include but not limited to computed tomography (CT), positron emission tomography (PET), PET/CT, magnetic resonance imaging (MRI);
• Skeletal or bone-only disease which is measurable by fludeoxyglucose (FDG) PET or PET/CT imaging will also be allowed
• Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy
• HER2 overexpression in the primary tumor or metastasis by immunohistochemistry (IHC) of 2+ or 3+, or documented gene amplification by fluorescence in situ hybridization (FISH) analysis; if overexpression is 2+ by IHC, then patients must have HER2 gene amplification documented by FISH
• Subjects must have a Performance Status Score (Southwest Oncology Group [SWOG]/Zubrod Scale) = 0, 1 or 2
• Patients must be off all immunosuppressive treatments such as chemotherapy or systemic steroid therapy a minimum of 14 days prior to initiation of study (i.e. first vaccination)
• Patients on trastuzumab and/or lapatinib must have a baseline left ventricular ejection fraction (LVEF) measured by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) equal to or greater than the lower limit of normal for the facility within 90 days of eligibility determination
• Men and women of reproductive ability must agree to contraceptive use during the entire study period
• Patients must have an expected survival of 6 months
• White blood cell (WBC) >= 3000/mm^3
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Hemoglobin (Hgb) >= 10 mg/dl
• Platelets >= 75,000/mm^3
• Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
• Total bilirubin =< 2.5 mg/dl
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 times upper limit of normal (ULN)
• Patients must be >= 18 years old

Exclusion Criteria

• Patients with any of the following cardiac conditions:

• Symptomatic restrictive cardiomyopathy;
• Unstable angina within 4 months prior to enrollment;
• New York Heart Association functional class III-IV heart failure on active treatment
• Patients with any contraindication to receiving rhuGM-CSF based products
• Patients with any clinically significant autoimmune disease uncontrolled with treatment
• Patients with a history of brain metastases must have a stable head imaging study within 30 days of eligibility determination; specifically, patients with active brain metastases will not be eligible for study
• Patients who are simultaneously enrolled in any other treatment study
• Pregnant or breast-feeding women

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

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Mary (Nora) Disis

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary Disis

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

Stanton SE, Eary JF, Marzbani EA, Mankoff D, Salazar LG, Higgins D, Childs J, Reichow J, Dang Y, Disis ML. Concurrent SPECT/PET-CT imaging as a method for tracking adoptively transferred T-cells in vivo. J Immunother Cancer. 2016 May 17;4:27. doi: 10.1186/s40425-016-0131-3. eCollection 2016.

Reference Type: DERIVED

PMID: 27190628 (View on PubMed)

Other Identifiers

NCI-2009-01591

Identifier Type: REGISTRY

Identifier Source: secondary_id

R01CA129517

Identifier Type: NIH

Identifier Source: secondary_id

View Link

6658

Identifier Type: -

Identifier Source: org_study_id