Clinical Trials /

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

NCT00971737

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Cyclophosphamide and Vaccine Therapy With or Without Trastuzumab in Treating Patients With Metastatic Breast Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: J0947 CDR0000653173
  • SECONDARY ID: P30CA006973
  • SECONDARY ID: JHOC-J0947
  • SECONDARY ID: NA_00024527
  • SECONDARY ID: GENENTECH-JHOC-J0947
  • NCT ID: NCT00971737

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
allogeneic GM-CSF-secreting breast cancer vaccineArm I
trastuzumabArm II
cyclophosphamideArm I

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Arm IActive ComparatorPatients 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.
  • cyclophosphamide
Arm IIExperimentalPatients 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.
  • cyclophosphamide

Eligibility 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
      
Maximum Eligible Age:120 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Toxicity as assessed by NCI CTCAE v3.0
Time Frame:3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Immune priming in in-vivo vaccine-site biopsies
Time Frame:3 years
Safety Issue:
Description:
Measure:Enumeration of CD8+ T cells specific for hTERT by ELISPOT
Time Frame:3 years
Safety Issue:
Description:
Measure:Characterization of the T-cell memory pool pre- and post-vaccination
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Unknown status
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center

Trial Keywords

  • stage IV breast cancer
  • male breast cancer

Last Updated

September 23, 2015