The Effect of TRA-8 on Ovarian Cancer Tissue

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Tong Zhou, MD, University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00711932
First received: July 3, 2008
Last updated: September 10, 2013
Last verified: June 2013
  Purpose

The goal of this study is to determine the apoptosis-inducing efficacy of TRA-8 in patient ovarian cancer tissues using a tissue slice technology. In addition, we want to evaluate the expression of apoptosis regulatory proteins using multiplex proteomic technology and its correlation with TRA-8-induced cytotoxicity in patient ovarian cancer tissues.


Condition
Ovarian Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Death Receptor-Mediated Apoptosis and Therapy Strategies in Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • Presence of TRA-8 apoptosis [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
    Apoptosis properties of TRA-8 will be analyzed in tissue collected from surgery using tissue slice technology.

  • Presence of apoptosis regulatory proteins [ Time Frame: At the time of surgery ] [ Designated as safety issue: No ]
    The presence of apoptosis regulatory properties will be analyzed in tissue collected from surgery using multiplex proteomic technology.


Enrollment: 478
Study Start Date: August 2008
Study Completion Date: January 2013
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Detailed Description:

Ovarian cancer remains highly lethal, with an estimated 25,580 new cases and 16,090 death per year in the US. The most common ovarian cancers arise from the surface epithelium of the ovary. Approximately 75% of patients with advanced-stage cancer are surgically incurable. While chemotherapy is a critical component of treatment, the pre-existing and induced chemoresistance of ovarian cancer cells is a major obstacle in treatment of patients with advanced disease. Novel strategies to enhance the established therapeutic Defective apoptosis has been proposed as one of the major mechanisms that lead to malignant transformation and resistance to therapeutics. Defective apoptosis may result from increased growth stimulation (oncogenes), decreased growth inhibition (tumor suppressor genes) or imbalanced apoptosis regulation. Alterations of the Bcl-2 family proteins have been reported to be associated with chemotherapy resistance in ovarian cancer cells.(1) Increased anti-apoptosis protein, Bcl-XL, may play a role in preventing apoptosis of ovarian cancer cells in response to chemotherapy. Conversely, high levels of pro-apoptosis protein, Bax, are associated with a favorable response to therapy. The role of these and other apoptotic regulatory proteins in sensitivity/resistance mechanisms to chemotherapy in patient's ovarian cancer cells are just beginning to be elucidated.

Precision cut tumor slices will be prepared from fresh primary ovarian tumor specimens using the Krumdieck tissue slicer, followed by ex vivo TRA-8 cytotoxicity assays on the tumor slices. Tumor-derived tissue slices may be used immediately in short term assays with no need to isolate or expand tumor cells, thus avoiding potential problems in maintaining cell viability or selecting variant cells during tumor dispersion or longer periods of in vitro cell culture. Demonstration of TRA-8-induced apoptosis using primary ovarian tumors in ex vivo tumor slice cytotoxicity assays can strengthen the rationale for this therapy in this tumor type and may be used to select patients who would most likely benefit from TRA-8 therapy. The sensitivity of ovarian patient tumors to TRA-8, paclitaxel, and carboplatin will be evaluated in tumor slice cytotoxicity assays as single agents and in combination. Slices from different treatment conditions will be paraffin-embedded or frozen for immunohistochemical evaluation.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with histologically confirmed epithelial carcinoma of the ovary or of extra-ovarian origin, any histologic subtype or stage 19 years of age or older.

Criteria

Inclusion Criteria:

  • Patients must have suspected ovarian cancer and must be a candidate for surgery.
  • Patients must have provided a signed consent form.
  • Patients must have extra tumor at the time of surgery that is appropriate for tumor slicing.
  • Patients must be at least 19 years of age.
  • Patients must have histologically confirmed epithelial carcinoma of the ovary or of extra-ovarian origin, any histologic subtype or stage.

Exclusion Criteria:

  • Patients who have received any prior therapy for ovarian cancer.
  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: NCT00711932

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
Sponsors and Collaborators
University of Alabama at Birmingham
Investigators
Principal Investigator: Tong Zhou, M.D. University of Alabama at Birmingham
  More Information

No publications provided

Responsible Party: Tong Zhou, MD, Associate Professor of Medicine, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00711932     History of Changes
Other Study ID Numbers: F080328006/UAB0802, ROI CA 123197-01
Study First Received: July 3, 2008
Last Updated: September 10, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by University of Alabama at Birmingham:
Ovarian Cancer
TRA-8
Monoclonal Antibody
Tissue Slice Technology

Additional relevant MeSH terms:
Ovarian Neoplasms
Adnexal Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms
Neoplasms by Site
Ovarian Diseases
Urogenital Neoplasms

ClinicalTrials.gov processed this record on October 29, 2014