Vaccine Therapy in Treating Patients With Stage IV Breast Cancer

NCT00791037 | Completed Phase 1 Results

• 3 other identifiers: 6658NCI-2009-01591R01CA129517
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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)

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Evaluate Toxicity of Infusing HER2-specific T Cells as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0

  Patients are monitored for the development of end organ damage by assessing adverse events with serum chemistries, liver function studies, complete blood counts, urine analysis and physical exams. All adverse events for all systems are graded on a scale of 1-5 and attribution is assigned. There are DLT criteria. DLT is defined as any incidence of Grade 3 hematologic and non-hematologic toxicity (excluding: fever, hypoxia, and urticaria) Thus, if a subject develops a Grade 3 toxicity (excluding those listed in Table 4) will be considered excessive toxicity and no further dose escalations will occur.

  Up to 4 months after first booster vaccine

Secondary Outcomes (3)

• Proportion of Patients Whose T Cells Persist at a Level the Same or Greater as the Level After the Final T Cell Infusion and Subsequent Booster Immunizations as Assessed by IFN-gamma (IFN-g) ELISPOT

  Up to 2 year following the last infusion

• Development of CD4+ and CD8+ Epitope Spreading

  Up to 2 years

• Response of Skeletal or Bone-only Disease by FDG-PET and According to European Organization for Research and Treatment for Cancer (EORTC)

  Up to 2 years

Study Arms (1)

Treatment (vaccine therapy)

EXPERIMENTAL

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.

Biological: HER-2/neu peptide vaccine; Procedure: leukapheresis; Biological: ex vivo-expanded HER2-specific T cells; Drug: cyclophosphamide; Biological: sargramostim; Other: laboratory biomarker analysis

Interventions

HER-2/neu peptide vaccine BIOLOGICAL

Given ID

Also known as: HER-2

Treatment (vaccine therapy)

leukapheresis PROCEDURE

Undergo leukapheresis

Treatment (vaccine therapy)

ex vivo-expanded HER2-specific T cells BIOLOGICAL

Given IV

Treatment (vaccine therapy)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (vaccine therapy)

sargramostim BIOLOGICAL

Given ID

Also known as: GM-CSF, Leukine, Prokine

Treatment (vaccine therapy)

laboratory biomarker analysis OTHER

Correlative study

Treatment (vaccine therapy)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 27190628 DERIVED

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

Leukapheresis; Cyclophosphamide; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Limitations and Caveats

All Other Adverse Events are reported regardless of attribution.

Results Point of Contact

• Title: Dr. Mary L. Disis
• Organization: University of Washington

ndisis@u.washington.edu

206-543-8557

Study Officials

• Mary Disis

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 13, 2008
• First Posted: November 14, 2008
• Study Start: October 1, 2008
• Primary Completion: July 1, 2013
• Study Completion: December 1, 2014
• Last Updated: May 25, 2017
• Results First Posted: May 25, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)