Clinical Trial: A Pilot Study of Celecoxib in Patients With Grade 2 or 3 Uterine Cancers

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Pilot Phase II Trial of Celecoxib in Patients With Grade 2 or 3 Endometrioid-type, Clear Cell, and Papillary Serous Uterine Cancers

Brief Summary: Expression of COX-II has been identified in many types of human cancers. Uterine cancer is the most common gynecologic cancer in the US and there has been an increase in uterine cancer deaths over the past decade mainly due to the difficulty in treating recurrences in the more aggressive histologic types. The study co-investigators have also identified COX-II expression in grade 2 and 3 endometrioid-type, clear cell, and papillary serous types of uterine cancers. Upregulation of COX-II may control the cell cycle by regulating the proliferative capacity of neoplastic endometrial cells. This is a Phase II pre-post intervention comparison study in eligible patients looking at the effects of a COX-II inhibitor on uterine cancer. The patients whose endometrial biopsy shows grade 2 or 3 endometrioid-type, clear cell, and papillary serous types of uterine cancers will be put on a selective COX-II inhibitor, Celebrex (Celecoxib) until the day of their surgery. We hypothesize that Celecoxib will downregulate the expression of COX-II in these tumor types as it does in other similar tumors. We also hypothesize that apoptosis, as measured with the TUNEL assay, will be increased in areas with less COX-II expression and should be inversely proportional to cellular p21 expression. We hypothesize COX-related gene expression will be altered thus suggesting an up- or down-regulation of these genes in the end-organ tissue. Documenting downregulation of COX-II enzyme and altered gene expression in endometrial carcinoma after treatment with Celecoxib may result in further prospective studies using selective COX-II inhibitors as effective, well-tolerated chemotherapeutic agents in these uterine cancers that are resistant to many current therapies.

Detailed Summary:

Endometrial cancer is the most common gynecologic cancer in the United States. The number of deaths from endometrial cancer has risen 128% since 1987. In 2001, an estimated 38,300 women will develop endometrial cancer (ACS Facts and Figures) and an estimated 6,600 women will die from endometrial cancer. Preinvasive and well-differentiated endometrial cancers are hormonally driven and often cured with surgery alone. Higher-grade tumors are usually not hormonally driven and proliferate via unknown mechanisms. These tumors are largely responsible for the rising death rate. Responses to toxic treatment protocols for recurrent endometrial cancer are dismal. Unfortunately, these post-menopausal women also often have comorbidities, which limit their eligibility for current chemotherapy and radiotherapy treatments.

Expression of COX-II has been identified in many human cancers including: colon cancer, gastric cancer, esophogeal cancer, bladder cancer, head and neck cancer, liver cancer, pancreatic cancer, prostate cancer and breast cancer. COX-II expression is also strongly expressed in the primary tumor and metastasic site in human cervical cancer. COX-II may influence cell cycle control by upregulating the proliferative capacity of neoplastic endometrial cells. Furthermore, COX-II inhibitors inhibit tumor proliferation even in cells that do not express COX. This suggests an alternative mechanism of action not yet defined that may play a role in inhibiting the growth of cancer tissue.

The enhanced expression of COX-II has led investigators to use COX-II inhibitors in the prevention and/or treatment of colon and prostate cancers both in vivo and in vitro. Celecoxib is now FDA approved for chemoprevention of colon cancer in familial adenomatous polyposis patients. If it can be shown that COX-II is downregulated by COX-II inhibitors
Sponsor: Mark H. Einstein

Current Primary Outcome: To compare COX-II expression in grade 2 or grade 3 uterine cancers treated with Celecoxib, following endometrial biopsy (pre-intervention) and after hysterectomy (post-intervention)

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • o To confirm the safety and tolerability of Celecoxib in this patient population.
  • o To evaluate alterations in the cell cycle pre- and post-intervention with Celecoxib.
  • o To evaluate apoptosis pre- and post-intervention using the TUNEL method.
  • o To evaluate the relationship between COX-II expression, apoptosis, p21 with clinical prognostic factors.
  • o To evaluate COX-related gene expression in the post-intervention uterine tissue by RT-PCR and compare to untreated matched controls.


Original Secondary Outcome: Same as current

Information By: Montefiore Medical Center

Dates:
Date Received: September 30, 2005
Date Started: April 2003
Date Completion:
Last Updated: April 22, 2012
Last Verified: April 2012