Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patients With High-Risk or Metastatic Breast Cancer

NCT00847171 | Completed Phase 2 Results

• 4 other identifiers: J0885P30CA006973NA_00021048CDR0000634155
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: 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. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vaccines made from gene-modified tumor cells may help the body build an immune response to kill tumor cells. Giving trastuzumab together with cyclophosphamide and vaccine therapy may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving trastuzumab together with cyclophosphamide and vaccine therapy in treating patients with high-risk or metastatic breast cancer.

Conditions

Breast Cancer

Keywords

male breast cancer; stage II breast cancer; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV breast cancer; HER2-positive breast cancer

Outcome Measures

Primary Outcomes (2)

• Safety as Assessed by Number of Participants Experiencing Toxicity

  Safety as assessed by number of participants who experienced drug-related local and systemic toxicity, as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v3.0) in response to CY-modulated immunization with a novel breast cancer vaccine in the setting of weekly Trastuzumab therapy.

  4 years

• Number of Participants With Immunologic Response as Determined by Delayed-type Hypersensitivity (DTH) Response to HER2/Neu-derived Peptides

  4 years

Secondary Outcomes (1)

• Clinical Benefit as Assessed by Number of Participants With Progression-free Survival

  4 years

Study Arms (1)

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

EXPERIMENTAL

Participants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine

Biological: allogeneic GM-CSF-secreting breast cancer vaccine; Biological: trastuzumab; Drug: cyclophosphamide; Other: flow cytometry; Other: immunoenzyme technique; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: pharmacological study; Procedure: biopsy

Interventions

allogeneic GM-CSF-secreting breast cancer vaccine BIOLOGICAL

Day 0 : Allogeneic GM-CSF-secreting Breast Cancer Vaccine administered as: 12 intradermal injections of a divided total dose of 5 x108 cells.

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

trastuzumab BIOLOGICAL

Patient HAS received prior Trastuzumab within the last two weeks, give Trastuzumab 2 mg/kg weekly on Day -1 for 5 weeks. Patient has NOT received Trastuzumab within the last two weeks, give On Cycle 1, Day -1 ONLY, Loading dose 4 mg/kg

Also known as: Herceptin

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

cyclophosphamide DRUG

Cyclophosphamide 200mg/m2 IV in NS 100ml over 30 minutes on Day -1 ONLY. Note: there are no dose modifications for Cyclophosphamide.

Also known as: Cytoxan

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

flow cytometry OTHER

Samples will be analyzed by flow cytometry using Cell Quest software

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

immunoenzyme technique OTHER

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

immunohistochemistry staining method OTHER

Measuring Immune Priming In Vivo By Vaccine Site Biopsies

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

laboratory biomarker analysis OTHER

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

pharmacological study OTHER

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

biopsy PROCEDURE

skin biopsy to be performed on day 3 and day 7 for cycle 1 and 3 only

Trastuzumab, Cyclophosphamide, and a Breast Tumor Vaccine

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed adenocarcinoma of the breast, meeting one of the following criteria: * Metastatic disease * High-risk disease, defined as early-stage disease with pathologic involvement of locoregional lymph nodes * Patients who are/will be receiving standard adjuvant trastuzumab \[Herceptin®\] for high-risk disease will participate in this study during the single-agent trastuzumab portion of their therapy * No clinical or radiographical evidence of active disease * Not eligible for therapy of known curative potential for metastatic breast cancer * HER2/neu-overexpressing disease, defined as HER2/neu positive by IHC 3+ staining or by FISH+ amplification * Stable CNS disease allowed provided it has been adequately treated and is not under active treatment * Hormone receptor status not specified PATIENT CHARACTERISTICS: * Menopausal status not specified * ECOG performance status 0-1 * ANC \> 1,000/mm\^3 * Platelet count \> 100,000/mm\^3 * Serum creatinine \< 2.0 mg/dL * Serum bilirubin ≤ 2.0 mg/dL (unless elevation is due to known Gilbert's syndrome) * AST/ALT ≤ 2 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 5 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * Cardiac ejection fraction normal by MUGA OR ≥ 45% by ECHO * No other malignancies within the past 5 years, except for carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, or superficial bladder cancer * No prior or currently active autoimmune disease\* requiring management with systemic immunosuppression, including any of the following: * Inflammatory bowel disease * Systemic vasculitis * Scleroderma * Psoriasis * Multiple sclerosis * Hemolytic anemia or immune-mediated thrombocytopenia * Rheumatoid arthritis * Systemic lupus erythematosus * Sjögren syndrome * Sarcoidosis * Other rheumatologic disease * No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest * HIV-negative * No evidence of active acute or chronic infection * No uncontrolled medical problems * No active major medical or psychosocial problems that could be complicated by study participation * No corn allergy * No known severe hypersensitivity to trastuzumab (except for mild to moderate infusion reactions that are easily managed and do not recur) NOTE: \*Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed PRIOR CONCURRENT THERAPY: * Any number of prior chemotherapy regimens for metastatic breast cancer allowed * Prior or concurrent trastuzumab in the adjuvant or metastatic setting allowed * More than 28 days since prior and no concurrent systemic oral steroids * Topical, ocular, or nasal steroids allowed * More than 28 days since prior and no concurrent chemotherapy, radiotherapy, or biologic therapy (except trastuzumab) * More than 28 days since prior and no concurrent participation in another investigational clinical trial involving a new drug * Concurrent endocrine therapy or bisphosphonates allowed

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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231-2410, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Breast Neoplasms, Male

Interventions

Trastuzumab; Cyclophosphamide; Flow Cytometry; Immunoenzyme Techniques; Immunohistochemistry; Biopsy

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; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Histological Techniques; Cytodiagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Leisha Emens
• Organization: Johns Hopkins University

emensle@jhmi.edu

Study Officials

• Leisha A. Emens, MD, PhD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  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

Study Record Dates

• First Submitted: February 18, 2009
• First Posted: February 19, 2009
• Study Start: December 1, 2008
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: September 26, 2018
• Results First Posted: September 26, 2018

Record last verified: 2018-09

Locations

US (1)