Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00971737
Recruitment Status : Completed
First Posted : September 4, 2009
Results First Posted : March 12, 2019
Last Update Posted : April 24, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 63 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
Actual Primary Completion Date : March 2016
Actual Study Completion Date : March 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Active Comparator: Cyclophosphamide and Vaccine only
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: Cyclophosphamide, Vaccine and Trastuzumab
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Toxicity as Assessed by Number of Grade 3 or 4 Adverse Events [ Time Frame: 3 years ]
    Number of grade 3 or 4 nonhematologic toxicity (except alopecia), or any grade 4 hematologic toxicity as defined by NCI CTCAE v3.0

  2. Clinical Benefit (CB) as Assessed by Progression Free Survival at Six Months [ Time Frame: 6 months post-intervention ]
    Progression-free survival is measured as percentage of participants with stable disease or complete response, as defined by RECIST criteria, six months after receiving last vaccination. Progressive disease (PD) will be defined by the appearance of a new lesion, or by an increase of at least 20% in the sum of the longest diameter of target lesions, taking as a reference that smallest sum longest diameter recorded since the study intervention began. In the case of bone lesions, progressive disease will be established after eight weeks of increasing or new lesions if there is subjective progressive disease as noted by increasing bone pain or decreasing performance status. These observations must be present for at least two measurement periods separated by at least four weeks.

  3. HER-2/Neu-specific Immune Responses as Measured by Number of Participants With Positive for Delayed-type Hypersensitivity (DTH) Response [ 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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Layout table for location information
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
Layout table for investigator information
Principal Investigator: Leisha A. Emens, MD, PhD Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00971737     History of Changes
Other Study ID Numbers: J0947
P30CA006973 ( U.S. NIH Grant/Contract )
JHOC-J0947
NA_00024527
GENENTECH-JHOC-J0947
CDR0000653173 ( Other Identifier: other )
First Posted: September 4, 2009    Key Record Dates
Results First Posted: March 12, 2019
Last Update Posted: April 24, 2019
Last Verified: April 2019

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

Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vaccines
Cyclophosphamide
Sargramostim
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
Antineoplastic Agents, Immunological