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Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT00971737
Recruitment Status : Unknown
Verified September 2015 by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.
Recruitment status was:  Active, not recruiting
First Posted : September 4, 2009
Last Update Posted : September 25, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description
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Brief Summary:

RATIONALE: Vaccines made from gene-modified tumor cells may help the body build an effective immune response to kill tumor cells. Biological therapies, such as cyclophosphamide and trastuzumab, may increase the number of immune cells and make the immune response stronger. It is not yet known whether giving cyclophosphamide together with vaccine therapy is more effective with or without trastuzumab in treating patients with metastatic breast cancer.

PURPOSE: This randomized phase II trial is studying the side effects of giving cyclophosphamide together with vaccine therapy and to see how well it works compared with giving cyclophosphamide and vaccine therapy together with trastuzumab in treating patients with metastatic breast cancer.


Condition or disease Intervention/treatment Phase
Breast Cancer Biological: allogeneic GM-CSF-secreting breast cancer vaccine Biological: trastuzumab Drug: cyclophosphamide Phase 2

Detailed Description:

OBJECTIVES:

Primary

  • To evaluate the safety of cyclophosphamide-modulated vaccination with vs without trastuzumab in patients with breast cancer that does not overexpress HER-2/neu.
  • To compare the clinical benefit of cyclophosphamide-modulated vaccination with vs without trastuzumab in these patients.
  • To measure HER-2/neu-specific CD4+ and CD8+ T-cell immunity by delayed-type hypersensitivity (DTH) and ELISPOT.
  • To measure the pharmacodynamics of CD4+CD25+ regulatory T cells by flow cytometry.

Secondary

  • To assess the impact of trastuzumab on immune priming in vivo by immunohistochemistry of vaccine-site biopsies at day +3 and day +7 of courses 1 and 3 on the two study arms, comparing cellular infiltrates to those seen in previous preclinical and clinical models.
  • To measure hTERT-specific CD8+ T-cell immunity by ELISPOT.
  • To characterize the peripheral-memory T-cell pool.

Tertiary

  • To determine baseline and change in vaccine site-draining lymph node immunohistology and gene expression profile.
  • To develop the tandem tetramer/CD107a cytotoxicity assay for HER-2/neu-specific CD8+ T cells.
  • To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
  • Arm II: Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.

Skin punch and lymph node biopsies are collected at baseline and on days +3 and +7 of courses 1 and 3 for biomarker analysis.

After completion of study treatment, patients are followed periodically.


Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label Comparative Study of Combination Therapy With Cyclophosphamide and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine With or Without Trastuzumab for the Treatment of Metastatic Breast Cancer That Does NOT Over-express HER-2/Neu
Study Start Date : July 2009
Estimated Primary Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Arm I
Patients receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic GM-CSF-secreting breast cancer vaccine intradermally on day 0. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
 Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Given intradermally

Drug: cyclophosphamide
Given IV
Experimental: Arm II
Patients receive cyclophosphamide and the vaccine as in arm I and trastuzumab IV over 30-90 minutes on day -1. Courses repeat every 4-6 weeks for 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth vaccination at 6-8 months.
 Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Given intradermally

Biological: trastuzumab
Given IV

Drug: cyclophosphamide
Given IV


Outcome Measures
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Primary Outcome Measures :
  1. Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 3 years ]
  2. Progression-free survival at 6 months [ Time Frame: 3 years ]
  3. HER-2/neu-specific immune responses [ Time Frame: 3 years ]
  4. Pharmacodynamics of peripheral CD4+CD25+ regulatory T cells [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. Immune priming in in-vivo vaccine-site biopsies [ Time Frame: 3 years ]
  2. Enumeration of CD8+ T cells specific for hTERT by ELISPOT [ Time Frame: 3 years ]
  3. Characterization of the T-cell memory pool pre- and post-vaccination [ Time Frame: 3 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the breast

    • Does not overexpress HER-2/neu, defined as FISH negative or 0, 1+, or 2+ by IHC
    • Stage IV disease
  • Must not be eligible for therapy of known curative potential for metastatic breast cancer
  • Measurable or evaluable disease
  • Stable CNS disease allowed provided that it's adequately treated and 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
  • Platelets > 100,000/mm^3
  • Serum bilirubin < 2.0 mg/dL (unless due to Gilbert syndrome)
  • AST and ALT < 2 times upper limit of normal (ULN)
  • Alkaline phosphatase < 5 times ULN
  • Serum creatinine < 2.0 mg/dL
  • Ejection fraction normal by MUGA OR ≥ 50% by echocardiogram
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative
  • Asthma or chronic obstructive pulmonary disease that does not require daily systemic corticosteroids allowed

  • No prior or concurrent 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
    • Sjogren syndrome
    • Sarcoidosis
    • Other rheumatologic disease
  • No other malignancies within the past 5 years, except carcinoma in situ of the cervix, superficial nonmelanoma skin cancer, superficial bladder cancer, or tamoxifen-related endometrial cancer that has been adequately treated
  • No active major medical or psychosocial problems that could be complicated by study participation
  • No symptomatic intrinsic lung disease or extensive tumor involvement of the lungs resulting in dyspnea at rest
  • No uncontrolled medical problems
  • No evidence of active acute or chronic infection
  • No known severe hypersensitivity to trastuzumab, except mild to moderate infusion reactions that are easily managed and do not recur
  • No allergy to corn

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

  • More than 28 days since prior and no other concurrent chemotherapy, radiation therapy, or biologic therapy (except trastuzumab)

    • Concurrent endocrine therapy and supportive therapy with bisphosphonates allowed
  • More than 28 days since prior and no other concurrent participation in an investigational new drug trial

  • More than 28 days since prior and no other concurrent systemic oral steroids

    • Topical, ocular, and nasal steroids allowed
  • No prior vaccination with the allogeneic GM-CSF-secreting breast tumor vaccine
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00971737


Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
National Cancer Institute (NCI)
Investigators
Principal Investigator: Leisha A. Emens, MD, PhD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
More Information
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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00971737     History of Changes
Other Study ID Numbers: J0947 CDR0000653173
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0947
NA_00024527
GENENTECH-JHOC-J0947
First Posted: September 4, 2009    Key Record Dates
Last Update Posted: September 25, 2015
Last Verified: September 2015

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
stage IV breast cancer
male breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vaccines
Cyclophosphamide
Trastuzumab
Immunologic Factors
 Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists