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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Sidney Kimmel Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00971737
First received: September 3, 2009
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Breast Cancer
Biological: allogeneic GM-CSF-secreting breast cancer vaccine
Biological: trastuzumab
Drug: cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • Toxicity as assessed by NCI CTCAE v3.0 [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]
  • Progression-free survival at 6 months [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • HER-2/neu-specific immune responses [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Pharmacodynamics of peripheral CD4+CD25+ regulatory T cells [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immune priming in in-vivo vaccine-site biopsies [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Enumeration of CD8+ T cells specific for hTERT by ELISPOT [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • Characterization of the T-cell memory pool pre- and post-vaccination [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: July 2009
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00971737

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Maureen Berg, RN, OCN    443-287-6602    Mberg1@jhmi.edu   
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Leisha A. Emens, MD, PhD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00971737     History of Changes
Other Study ID Numbers: J0947 CDR0000653173, P30CA006973, JHOC-J0947, NA_00024527, GENENTECH-JHOC-J0947
Study First Received: September 3, 2009
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 01, 2014