Know Cancer

or
forgot password

A Phase I Study Investigating Multiple Injections of Autologous CD34+ Derived Dendritic Cells Transduced With an Adenovirus Vector Expressing Inactivated HER-2/Neu in Patients With Metastatic Breast Cancer


Phase 1
16 Years
80 Years
Not Enrolling
Female
Breast Neoplasms

Thank you

Trial Information

A Phase I Study Investigating Multiple Injections of Autologous CD34+ Derived Dendritic Cells Transduced With an Adenovirus Vector Expressing Inactivated HER-2/Neu in Patients With Metastatic Breast Cancer


Following written, informed consent, consecutive cohorts of 3-6 patients, up to a maximum of
18 patients, will be treated at increasing dose levels based on a modified Fibonacci scheme.
Peripheral blood progenitor cells will be obtained from each patient following cytokine
mobilization (with GM-CSF and G-CSF). Selected CD34+ cells are then cultured with human
GM-CSF, human TNF╬▒, Flt-3 ligand and human interleukin-4. The CD34+ derived dendritic cells
are then transduced with an adenovirus expressing rat HER2/neu. These transduced DCs are
then injected intradermally into the patient. Patients will be injected with the AdHER2/neu
transduced DCs every 21 days for a total of three treatment cycles. The starting dose of
dendritic cells will be 10 X 10^6 DCs. If none of the initial three patients treated at
this dose experiences dose limiting toxicity (DLT) then a new cohort of three patients will
be treated at a second dose level of 50 X 10^6 DCs. If any patient experiences DLT then up
to six patients will be treated at the current dose level; if 2/6 or fewer patients
experience DLT, we will escalate to the to the second dose level. If 3 or more patients
experience DLT, the maximum tolerated dose will be deemed as exceeded and a second cohort of
3 patients will be treated at a 10 fold dose reduction of the initial dose level. The third
dose level will consist of 100 x 10^6 DCs. All treatments will occur in the out-patient
setting and patients will be seen prior to each injection and then monthly for at least
three months following the last injection of AdHER2/neu DCs.


Inclusion Criteria:



- Patients with metastatic breast cancer who are HER2/neu positive (3+ by
immunohistochemistry or FISH positive) and either

1. currently receiving hormonal therapy or are candidates for such or

2. being considered for trastuzumab or

3. their cancer has progressed on trastuzumab

Exclusion Criteria:

Patients are excluded from the study if they meet any one of the following criteria:

- Age less than 16 years.

- Pregnant or lactating female.

- Previous malignancy other than non-melanoma skin cancer.

- More than three prior courses of cytotoxic chemotherapy for metastatic disease.

- Concurrent use of chemotherapy, immunotherapy, or gene therapy. Concurrent hormonal
therapy (tamoxifen, aromatase inhibitors or exemestane) is permitted.

- Treatment with trastuzumab within 16 weeks prior to first dose of vaccine therapy.

- Documented central nervous system metastases.

- Patients with any an acute illness that would interfere with the mobilization of stem
cells or the administration of vaccination cellular therapy (ie. unstable angina,
renal or liver failure, or severe chronic obstructive airways disease) are
ineligible.

- Any patients requiring concurrent immunosuppressive therapy (eg. corticosteroids)

- Patients with a life expectancy of less than six months.

- ECOG performance status of >2.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the maximum tolerated dose (MTD) and/or the maximum attainable dose (MAD) of a vaccine consisting of human autologous CD34+ DCs transduced by AdHER-2.1

Principal Investigator

Levine Mark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Hamilton Health Sciences Corporation

Authority:

Canada: Health Canada

Study ID:

file#9427-HO778-34C

NCT ID:

NCT00197522

Start Date:

October 2004

Completion Date:

May 2012

Related Keywords:

  • Breast Neoplasms
  • breast cancer
  • vaccination
  • dendritic cells
  • HER-2
  • CD34+ stem cells
  • Breast Neoplasms
  • Neoplasms

Name

Location