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Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer

Phase 1
18 Years
Open (Enrolling)
Breast Cancer

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Trial Information

Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer

T cells can penetrate virtually every biologic space and have the power to dispose of normal
or malignant cells as seen in viral and autoimmune diseases and in the rare spontaneous
remissions of cancer. However, T cells are easily tolerized to self or tumor antigens and
"immune surveillance" has manifestly failed in every cancer that is clinically apparent. It
is the goal of this study to supply the specificities and affinities to patient T cells
without regard for their "endogenous" T cell receptor repertoire, directed by
antibody-defined recognition to kill malignant cells based on their expression of antigen.
We will achieve this by preparing chimeric IgCD28TCR genes in mammalian expression vectors
to yield "designer T cells" from normal patient cells. Prior studies in model systems
demonstrated that recombinant IgCD28TCR could direct modified T cells to respond to antigen
targets with IL2 secretion, cellular proliferation, and cytotoxicity, the hallmarks of an
effective, self-sustaining immune response.

It therefore becomes of paramount interest to extend these studies to a human system of
widespread clinical relevance to explore the clinical potential of this new technology. The
target antigen for these studies is carcinoembryonic antigen (CEA), which is prominently
expressed on tumors of the stomach, colon and rectum, breast, pancreas and other sites.

For the Phase Ia component, patients receive a single dose of gene-modified autologous T
cells on this dose-escalation trial. Doses are 10^9 and 10^10 modified T cells. Patients
are monitored for safety and response. Patients are on-study for one month after dosing.

For the Phase Ib component, patients receive a fixed dose of gene-modified T cells (10^11
cells), randomized to receive T cell growth factor interleukin 2 (+IL2) [Experimental] or
not (-IL2) [Control]. The IL2 is administered outpatient by continuous infusion for a
two-week period. On Day +2 and Day +10, the patient's tumor is biopsied to assess the
designer T cell presence in the tumor as a means of judging the benefit of added IL2.
Patients will also be followed for tumor response.

Inclusion Criteria:

- Must have cancer of the breast

- Must have metastatic or unresectable locally advanced disease

- Tumor must express CEA by tumor staining or by elevated serum CEA (>10 ng/ml)

- Must have measurable disease radiologically or by physical exam

- Must have failed potentially curative standard therapy

- Must be 18 years of age or older

- Good performance status (PS 0-1)

Exclusion Criteria:

- Requiring systemic steroids

- Serious medical conditions

- Concurrent malignancies

Type of Study:


Study Design:

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

Outcome Measure:

Phase Ia:Determine the safety of using modified T-cells by documenting the type and severity of any side effects and establishing the maximum tolerated dose (MTD).

Outcome Time Frame:

1 Month

Safety Issue:


Principal Investigator

Richard P Junghans, PhD, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roger Williams Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

May 2008

Completion Date:

December 2013

Related Keywords:

  • Breast Cancer
  • Breast Cancer
  • T cells
  • Gene Transfer
  • Breast Neoplasms



Roger Williams Medical Center Providence, Rhode Island  02908-4735