A Pilot Study of Celecoxib in Patients With Grade 2 or 3 Uterine Cancers
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
|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|
- 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)
- 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.
|Study Start Date:||April 2003|
|Study Completion Date:||March 2004|
|Primary Completion Date:||March 2004 (Final data collection date for primary outcome measure)|
Please refer to this study by its ClinicalTrials.gov identifier: NCT00231829
|United States, New York|
|Montefiore Medical Center|
|Bronx, New York, United States, 10461|
|Principal Investigator:||Mark H Einstein, M.D., M.S.||Montefiore Medical Center and Albert Einstein College of Medicine|