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Breast CancerPhase 2NCT00847171

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

A Phase 2 study testing allogeneic GM-CSF-secreting breast cancer vaccine, trastuzumab and cyclophosphamide in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Breast Cancer
What is being tested?
allogeneic GM-CSF-secreting breast cancer vaccine, trastuzumab and cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
Dec 2008to Jun 2013
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    Baltimore, Maryland, 21231-2410

Other trials in United States

About this study

Official title: A Safety and Bioactivity Study of Combination Therapy With Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-Secreting Breast Tumor Vaccine for the Treatment of Patients With High Risk/ Metastatic HER-2/Neu- Overexpressing Breast Cancer With No Evidence of Disease

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.

Read the detailed description

OBJECTIVES:

Primary

  • To evaluate the safety of allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine in combination with trastuzumab (Herceptin®) and cyclophosphamide in patients with high-risk or metastatic HER2/neu-overexpressing breast cancer.
  • To measure the HER2/neu-specific CD4+ T-cell response by delayed-type hypersensitivity.
  • To measure the magnitude of HER2/neu-specific CD8+ T-cell responses by ELISPOT.

Secondary

  • To assess the impact of trastuzumab on immune priming in vivo by IHC.
  • To measure the impact of cyclophosphamide pretreatment on CD4+CD25+ regulatory T cells by flow cytometry.
  • To determine the time to disease progression.

Tertiary

  • To develop the tandem tetramer/CD107a cytotoxicity assay for HER2/neu-specific CD8+ T cells.
  • To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination.

OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day -1 of the first course of vaccination and continuing until the completion of the last course of vaccination. Patients also receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine intradermally on day 0. Treatment with cyclophosphamide and the vaccine repeats every 27-42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth course of cyclophosphamide and vaccine approximately 6-8 months after the first course.

Patients undergo delayed-type hypersensitivity testing and blood sample collection at baseline and periodically during study for immunologic laboratory studies. Blood samples are analyzed for serum GM-CSF levels by pharmacokinetic studies and for immune monitoring by ELISPOT and flow cytometry. Skin punch biopsies are also performed periodically and analyzed by IHC.

After completion of study treatment, patients are followed periodically.

Conditions
Breast Cancer
Being tested
allogeneic GM-CSF-secreting breast cancer vaccine, trastuzumab, cyclophosphamide, flow cytometry, immunoenzyme technique
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
Medical subject headings
Breast Neoplasms, Breast Neoplasms, Male

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • allogeneic GM-CSF-secreting breast cancer vaccineBiological

    Day 0 : Allogeneic GM-CSF-secreting Breast Cancer Vaccine administered as:

    12 intradermal injections of a divided total dose of 5 x108 cells.

  • trastuzumabBiological

    Also called Herceptin

    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

  • cyclophosphamideDrug

    Also called Cytoxan

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

  • flow cytometryOther

    Samples will be analyzed by flow cytometry using Cell Quest software

  • immunoenzyme techniqueOther

  • immunohistochemistry staining methodOther

    Measuring Immune Priming In Vivo By Vaccine Site Biopsies

  • laboratory biomarker analysisOther

  • pharmacological studyOther

  • biopsyProcedure or surgery

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

Study groups in NCT00847171
Study groupRoleWhat they receive
Trastuzumab, Cyclophosphamide, and a Breast Tumor VaccineExperimentalParticipants receive Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 4 years

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

    Measured: 4 years

Secondary outcomes (1)

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

    Number of participants without evidence of disease progression.

    Measured: 4 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2009 (estimated)
  2. Study startDec 2008
  3. Primary completionJun 2013
  4. Study completionJun 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00847171
Sponsor's protocol ID
J0885
Other IDs
P30CA006973, NA_00021048, CDR0000634155
Status last verified
Sep 2018
First submitted
18 Feb 2009
Last updated
26 Sep 2018

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing allogeneic GM-CSF-secreting breast cancer vaccine, trastuzumab and cyclophosphamide in people with Breast Cancer, run by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety as Assessed by Number of Participants Experiencing Toxicity (time frame: 4 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00847171.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2018.

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