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HER2-positive Breast CancerPhase 1NCT00228358

Cyclophosphamide or Denileukin Diftitox Followed By Expanding a Patient's Own T Cells in the Laboratory in Treating Patients With HER-2/Neu Overexpressing Metastatic Breast Cancer, Ovarian Cancer, or Non-Small Cell Lung Cancer Previously Treated With HER-2/Neu Vaccine

A Phase 1 study testing ex vivo-expanded HER2-specific T cells, cyclophosphamide and denileukin diftitox in people with HER2-positive Breast Cancer and Recurrent Breast Cancer, run by University of Washington 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

This phase I trial studies the safety and the ability to expand laboratory-treated T cells when given together with cyclophosphamide or denileukin diftitox in treating patients with human epidermal growth factor receptor (HER)-2/neu overexpressing metastatic breast cancer, ovarian cancer, or non-small cell lung cancer… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
ex vivo-expanded HER2-specific T cells, cyclophosphamide and denileukin diftitox
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteUnited States
Study dates
Jun 2003to May 2011
Phase
Phase 1
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with progressive HER2/neu overexpressing metastatic breast, ovarian, or non-small cell lung cancer not considered curable by conventional therapies, including trastuzumab
  • Extra-skeletal disease that can be accurately measured >= 10 mm by standard imaging techniques that can include but not limited to computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI)
  • Skeletal or bone-only disease which is measurable by Fludeoxyglucose F 18 (FDG) PET imaging will also be allowed
  • Patients with ovarian cancer may have measurable disease; however, their only indication of progression may be an abnormal CA-125
  • Patients must have documented HER-2/neu overexpression in their tumor (either primary or metastasis) as was required per the eligibility criteria of their original vaccination protocol
  • Patients must have received HER2-specific vaccinations while enrolled on a HER2 vaccine protocol approved at the University of Washington Human Subjects Division
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  • Patients must have undergone leukapheresis after vaccination through a protocol approved at the University of Washington Human Subjects Division and have product stored for clinical use
  • Subjects must have a Performance Status Score (Zubrod/Eastern Cooperative Oncology Group [ECOG] Scale) = 0 or 1
  • Patients can be currently receiving trastuzumab and/or lapatinib and/or hormonal therapy and/or bisphosphonate therapy
  • Patients on trastuzumab and/or lapatinib must have adequate cardiac function as demonstrated by multi gated acquisition (MUGA) scan or echocardiogram (ECHO) within 90 days of eligibility determination
  • Patients must be off all immunosuppressive treatments, and/or systemic steroid therapy, for at least 14 days prior to initiation of study treatment
  • Patients must be off chemotherapy and trastuzumab for at least 1 week prior to the first infusion of T cells
  • Men and women of reproductive ability must agree to contraceptive use during the study and for one month after the final T cell infusion
  • Patients with a history of brain metastases must have a stable head imaging study within 30 days of enrollment
  • White blood cells (WBC) >= 3000/mm^3
  • Absolute neutrophil count (ANC) >= 1000/mm^3
  • Hemoglobin (Hgb) >= 10 mg/dl
  • Platelets >= 75,000mm^3
  • Serum creatinine =< 2.0 mg/dl or creatinine clearance > 60 ml/min
  • Total bilirubin =< 2.5 mg/dl
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) =< 3 times ULN

Who cannot join

  • Concurrent enrollment in other treatment studies
  • Patients with any of the following cardiac conditions:
  • Symptomatic restrictive cardiomyopathy
  • Unstable angina within the last 4 months prior to enrollment
  • New York Heart Association functional class III-IV heart failure on active treatment
  • Patients with any clinically significant autoimmune disease uncontrolled with treatment
  • Pregnant or breast-feeding women
  • Known history of hypersensitivity to diphtheria toxin or interleukin (IL)-2 (only for subjects enrolled in Group B)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase I Study of Infusion of HER-2/Neu Specific T Cells in Patients With Advanced Stage HER-2/Neu Expressing Cancers Who Have Received a HER-2/Neu Vaccine

This phase I trial studies the safety and the ability to expand laboratory-treated T cells when given together with cyclophosphamide or denileukin diftitox in treating patients with human epidermal growth factor receptor (HER)-2/neu overexpressing metastatic breast cancer, ovarian cancer, or non-small cell lung cancer previously treated with HER-2/neu vaccine. Laboratory-expanded T cells may help the immune system in different ways and stop tumor cells from growing. 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. Biological therapy, such as denileukin diftitox, may stimulate the immune system in different ways and stop tumor cells from growing. Giving laboratory-treated T cells together with cyclophosphamide or denileukin diftitox may allow the immune system to kill more tumor cells

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the feasibility of expanding HER2 specific T cells ex vivo for infusion into subjects who have advanced HER2 overexpressing cancer.

II. To assess the toxicity associated with infusing autologous HER2 specific T cells into patients using either a single dose of cyclophosphamide or ONTAK (denileukin diftitox) prior to T cell infusion.

SECONDARY OBJECTIVES:

  1. To investigate to what extent HER2 specific T cell immunity can be boosted in individuals treated with a single dose of cyclophosphamide of ONTAK followed by infusion of autologous HER2 specific T cells.

II. To investigate the potential anti-tumor effects of HER2 specific T cells in patients with HER2 overexpressing advanced-stage cancers.

III. To evaluate how long tumor antigen specific T cell immune augmentation persists in vivo after a single dose of cyclophosphamide or ONTAK followed by infusion of autologous HER2 specific T cells.

OUTLINE: This is a dose-escalation study of ex vivo-expanded HER2-specific T cells. Patients are assigned to 1 of 2 treatment groups.

GROUP A: Patients receive low-dose cyclophosphamide intravenously (IV) on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.

GROUP B: Patients receive ONTAK (denileukin diftitox) IV over 1 hour on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.

After completion of study treatment, patients are followed periodically.

Being tested
ex vivo-expanded HER2-specific T cells, cyclophosphamide, denileukin diftitox, flow cytometry, immunoenzyme technique
Medical subject headings
Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Ovarian Epithelial

What participants receive

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

  • ex vivo-expanded HER2-specific T cellsDrug

    Laboratory-expanded T cells, given IV

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given IV

  • denileukin diftitoxBiological

    Also called DAB389 interleukin-2, DAB389 interleukin-2 immunotoxin, DAB389-IL2, DABIL2

    Given IV

  • flow cytometryOther

    Intracellular cytokine staining (correlative study)

  • immunoenzyme techniqueOther

    Also called immunoenzyme techniques

    ELIspot assay (correlative study)

Study groups in NCT00228358
Study groupRoleWhat they receive
Group A (cellular infusions after cyclophosphamide)ExperimentalPatients receive low-dose cyclophosphamide IV on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
Receives: Drug: ex vivo-expanded HER2-specific T cells; Drug: cyclophosphamide; Other: flow cytometry; Other: immunoenzyme technique
Group B (cellular infusions after ONTAK conditioning)ExperimentalPatients receive denileukin diftitox IV over 1 hour on day -1 and 3 escalating doses of autologous ex vivo-expanded HER2-specific T cells IV over 30 minutes on days 1, 10, and 20.
Receives: Drug: ex vivo-expanded HER2-specific T cells; Biological: denileukin diftitox; Other: flow cytometry; Other: immunoenzyme technique

What is being measured

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

  1. Feasibility of expanding HER2 specific T cells ex vivo to achieve a target T cell expansion of 1x10^10 HER2 specific T cells

    The procedure will be defined as feasible if the minimum target expansion of HER2 specific T cells is achieved in 2/3 expansions in 4/5 subjects within an arm.

    Measured: Up to day 40

  2. Safety of infusing HER2 specific T cells

    Toxicity grading will be evaluated according to the CTEP CTCAE v3.0 criteria. A specific dose of HER2 specific T cells will be defined as safe if 4 of 5 subjects in a study arm tolerate that dose without dose-limiting toxicity (DLT).

    Measured: Up to day 40

Secondary outcomes (5)

  1. Number of patients in whom the precursor frequency of antigen specific T cells is increased by 10-fold over baseline within one week after the last infusion

    Measured: Up to one week following last infusion

  2. Number of patients in whom an immune response is demonstrated if baseline immune response was below detection

    Measured: Up to one week following last infusion

  3. HER2 specific CD4+ or CD8+ precursor frequencies as assessed by cytokine flow cytometry or ELISPOT

    Measured: Up to 1 year following last infusion

  4. Anti-tumor effects of HER2 specific T cells as assessed by RECIST criteria

    Measured: Day 40

  5. Persistence of T cell immune augmentation in vivo after adoptive transfer of HER2 specific T cells

    Measured: Up to 1 year following last infusion

Timeline

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

  1. First posted28 Sep 2005 (estimated)
  2. Study startJun 2003
  3. Primary completionMay 2011

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 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00228358
Sponsor's protocol ID
6223
Other IDs
NCI-2009-01547
Status last verified
Nov 2014
First submitted
13 Sep 2005
Last updated
11 Nov 2014
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ex vivo-expanded HER2-specific T cells, cyclophosphamide and denileukin diftitox in people with HER2-positive Breast Cancer and Recurrent Breast Cancer, run by University of Washington 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?

The sponsor lists 21 inclusion and 8 exclusion criteria. 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 11 Nov 2014. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Feasibility of expanding HER2 specific T cells ex vivo to achieve a target T cell expansion of 1x10^10 HER2 specific T cells (time frame: Up to day 40). 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 NCT00228358.

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 11 Nov 2014.

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