Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Roger Williams Medical Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Roger Williams Medical Center
ClinicalTrials.gov Identifier:
NCT00673829
First received: May 5, 2008
Last updated: August 22, 2013
Last verified: August 2013
  Purpose

The purpose of this study is to collect data on the safety and effectiveness of 2nd generation designer T cells in patients with breast cancer. Designer T cells are prepared by collecting white blood cells from the participant, and then modifying these cells in the laboratory so that they recognize the tumor antigen (CEA). These modified cells are then given back to the participant so that they can attack and kill tumor cells.


Condition Intervention Phase
Breast Cancer
Biological: Gene Modified T Cells
Biological: Gene Modified T Cells and Interleukin 2
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase Ia/Ib Trial of 2nd Generation Anti-CEA Designer T Cells in Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Roger Williams Medical Center:

Primary Outcome Measures:
  • 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). [ Time Frame: 1 Month ] [ Designated as safety issue: Yes ]
  • Phase Ib: Determine optimal biologic dose (OBD) in terms of value of added interleukin 2. [ Time Frame: 1 Month ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Tumor Response [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
  • Pharmacokinetic [ Time Frame: 1 month ] [ Designated as safety issue: No ]
  • Pharmacodynamic [ Time Frame: 1 Month ] [ Designated as safety issue: No ]

Estimated Enrollment: 26
Study Start Date: May 2008
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase Ia Biological: Gene Modified T Cells
Gene Modified T Cells Phase Ia: One time infusion Modified TCells given through a vein in the arm or a catheter over a 30-60 minute period
Other Names:
  • Designer T-Cells
  • CEA
Experimental: Phase Ib: Control Biological: Gene Modified T Cells and Interleukin 2
One time infusion Modified T Cells without or with (randomized) continuous infusion outpatient interleukin 2 (IL2) for two weeks
Other Names:
  • Designer T-Cells
  • CEA

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00673829

Contacts
Contact: Robin A Davies, BA, BSN, RN 401-456-2419 rdavies@chartercare.org

Locations
United States, Rhode Island
Roger Williams Medical Center Recruiting
Providence, Rhode Island, United States, 02908
Contact: Robin A Davies, BA, BSN, RN    401-456-2419    rdavies@chartercare.org   
Principal Investigator: Richard P Junghans, PhD, MD         
Sponsors and Collaborators
Roger Williams Medical Center
Investigators
Principal Investigator: Richard P Junghans, PhD, MD Roger Williams Medical Center
  More Information

No publications provided

Responsible Party: Roger Williams Medical Center
ClinicalTrials.gov Identifier: NCT00673829     History of Changes
Other Study ID Numbers: 300-04
Study First Received: May 5, 2008
Last Updated: August 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Roger Williams Medical Center:
Breast Cancer
T cells
Gene Transfer

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 28, 2014