A Pilot Study of Celecoxib in Patients With Grade 2 or 3 Uterine Cancers - Full Text View

Sponsor:	Mark H. Einstein
Collaborator:	Pharmacia
Information provided by (Responsible Party):	Mark H. Einstein, Montefiore Medical Center
ClinicalTrials.gov Identifier:	NCT00231829

Purpose

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.

Condition	Intervention	Phase
Uterine Cancer	Drug: Celecoxib	Phase 2

Study Type:	Interventional
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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Uterine Cancer

Drug Information available for: Celecoxib

U.S. FDA Resources

Further study details as provided by Montefiore Medical Center:

Primary Outcome Measures:

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)

Secondary Outcome Measures:

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.

Estimated Enrollment:	23
Study Start Date:	April 2003
Study Completion Date:	March 2004
Primary Completion Date:	March 2004 (Final data collection date for primary outcome measure)

Show Detailed Description

Eligibility

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

Criteria

Inclusion Criteria:

Patients must be at least 18 years of age
Histologically confirmed uterine cancer of the following histologic types: grade 2 or grade 3 endometrioid-type, clear cell, or papillary serous types. The pre-therapy samples come from either an endometrial sampling (e.g. pipelle) or dilation and curettage of the uterus with or without hysteroscopy. Unstained slides of the primary tumor, a primary tumor block, or cytologic preparation must be available for review. COX-II expression is seen in the majority of patients with these tumor types. Effects of COX-II inhibitors occur even in the absence of COX-II expression and will be measured with other IHC staining, apoptosis studies and gene expression. Therefore, patients will not be tested for COX-II expression preoperatively in order to include them in the study.
Disease status: Only patients with clinical stage I or stage II disease will be eligible.
Negative urine pregnancy test in women of child-bearing potential (within 14 days of the initiation of Celebrex).
All eligible patients need to have a Zubrod/ECOG/GOG performance status ≤2 that permits surgery, with or without staging, as indicated.
All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Exclusion Criteria:

Celecoxib is contraindicated in patients with known hypersensitivity to Celecoxib. Celecoxib should not be given to patients who have demonstrated allergic-type reactions to sulfonamides. Celecoxib should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
Concurrent therapy: Patients who have had daily usage of any form of NSAID or aspirin prior to endometrial biopsy will be excluded from this study.
Selective COX-II inhibitors have some activity on the gastrointestinal mucosa. Although Celecoxib is not contraindicated in patients with peptic ulcer disease, these patients will be excluded to avoid any untoward gastrointestinal side effects.
There is no information regarding the use of Celecoxib in patients with advanced renal disease. Therefore, treatment with Celecoxib is not recommended in these patients.
Patient has impairment of hepatic, renal or hematologic function as defined by the following baseline laboratory values performed <= 4 weeks prior to the study:
- Serum SGOT and/or SGPT > 2.5 times the institutional upper limit of normal (IULN).
- Total serum bilirubin > 1.5 mg/dL.
- History of chronic active hepatitis or cirrhosis.
- Serum creatinine > 2.0 mg/dL.
- Platelets < 100,000/mm3
- Absolute neutrophil count (ANC) < 1500/mm3
- Hemoglobin < 8.0 g/dL
- PT/PTT within normal range
- Pregnant or nursing women are excluded. Women of child-bearing potential must agree to use a chemical or barrier contraceptive during the dosing portion of the study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00231829

Locations

United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10461

Sponsors and Collaborators

Mark H. Einstein

Pharmacia

Investigators

Principal Investigator:

Mark H Einstein, M.D., M.S.

Montefiore Medical Center and Albert Einstein College of Medicine

More Information

Publications:

Cao QJ, Einstein MH, Anderson PS, Runowicz CD, Balan R, Jones JG. Expression of COX-2, Ki-67, cyclin D1, and P21 in endometrial endometrioid carcinomas. Int J Gynecol Pathol. 2002 Apr;21(2):147-54.

Responsible Party:	Mark H. Einstein, Director, Clinical Research for Women's Health, Montefiore Medical Center
ClinicalTrials.gov Identifier:	NCT00231829 History of Changes
Other Study ID Numbers:	MMC-03-04-084
Study First Received:	September 30, 2005
Last Updated:	April 22, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Montefiore Medical Center:

Treatment
Uterine Papillary Serous Carcinoma
Clear Cell Carcinoma
COX-2 Inhibitors

Additional relevant MeSH terms:

Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Celecoxib
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

Pharmacologic Actions
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Therapeutic Uses
Central Nervous System Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 24, 2012