Identifying Genetic Markers That Predict Response to Paclitaxel in Patients With Newly Diagnosed Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer
Identifying Genetic Markers That Predict Response to Paclitaxel in Patients With Newly Diagnosed Stage III or Stage IV Ovarian Epithelial Cancer or Primary Peritoneal Cancer
RATIONALE: DNA analysis of tumor tissue from patients with cancer may help doctors predict
 how patients respond to treatment and plan the best treatment.

 PURPOSE: This laboratory study is identifying genetic markers that predict response to
 paclitaxel in patients with newly diagnosed stage III or stage IV ovarian epithelial cancer
 or primary peritoneal cancer.
OBJECTIVES:

 Primary

 -  Identify genetic markers of paclitaxel chemosensitivity and/or chemoresistance, using
 gene expression arrays, in patients with newly diagnosed stage III or IV ovarian
 epithelial cancer or primary peritoneal cancer treated with single-agent weekly
 paclitaxel followed by paclitaxel in combination with carboplatin.

 -  Correlate RNA expression levels with clinical response in patients treated with this
 regimen.

 Secondary

 -  Determine the response rate in patients treated with this regimen.

 -  Determine the progression-free survival and overall survival of patients treated with
 this regimen.

 -  Compare transcriptional profiles of primary tumors vs tissue obtained at second-look
 surgery in patients treated with this regimen.

 -  Identify differential expression between pre- and post-treatment tissue in patients
 treated with this regimen.

 OUTLINE: This is a pilot study.

 Pre- and post-chemotherapy tumor samples undergo transcriptional profiling using cDNA
 microarrays to identify gene overexpression. The gene expression profiles of
 paclitaxel-sensitive tumors are compared with those that are paclitaxel resistant to identify
 gene markers that are associated with response to paclitaxel.

 PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.
Inclusion Criteria:

 1. Patients with newly diagnosed histologically confirmed advanced stage (III & IV)
 epithelial ovarian cancer, fallopian tube or peritoneal cancer. --OR-- Patients with a
 suspected malignancy who are unsuitable candidates for surgery (i.e., those with
 medical co-morbidities, massive effusions, or tumor burden such that an optimal
 resection is unlikely) who undergo a core biopsy that is positive for malignancy.

 2. Patients who have undergone tumor reduction must have either stage III suboptimal (> 2
 cm residual) disease or stage IV disease.

 3. Patients may have had no prior chemotherapeutic regimen.

 4. Zubrod performance status of 0, 1, or 2.

 5. Patients must have recovered from effects of recent surgery. They should be free of
 significant infection.

 6. Patients must have adequate: Bone marrow function: WBC >/= than 3,000/microlitre,
 platelets > 100,000/microlitre, absolute neutrophil (ANC) count >/= than
 1.5/microlitre. Renal function: Creatinine </= 1.5 mg%. Hepatic function: Bilirubin
 </= 1.5 mg/dl, SGOT and alkaline phosphatase </= 3 X institutional normal.

 7. Patients must have adequate: Neurologic function: Pre-existing peripheral neurologic
 toxicity is allowed but limited to parasthesia and decreased vibratory sense without
 motor weakness. Intermittent constipation managed with laxatives is allowed, without
 evidence of bowel obstruction. Psychiatric function: Functions independently without
 evidence of delirium, confusion, suicidal ideation, or untreated depression.

 8. Patients who have signed an approved informed consent.

 Exclusion Criteria:

 1. Patients with borderline or grade 1 (low grade) tumors.

 2. Patients who have received any prior cytotoxic chemotherapy or radiotherapy.

 3. Patients with septicemia, severe infection, acute hepatitis, or gastrointestinal
 bleeding at the time of protocol entry.

 4. Patients with unstable angina or those who have had a myocardial infarction within the
 past six months. Patients with evidence of abnormal cardiac conduction (e.g., bundle
 branch block, heart block, etc.) are eligible if their disease has been stable for the
 past six months.

 5. Patients whose circumstances do not permit completion of the study or the required
 follow-up.

 6. Patients with a history of another malignancy within 5 years. Patients who have had a
 prior malignancy but remain continuously free of recurrent or persistent disease for
 more than 5 years may be entered in the study after consultation with the study chair.

 7. Patients with significant pre-existing cardiac disease (NYHA class III-IV) will be
 excluded.