Folate Receptor in Diagnosing Ovarian Cancer Using Serum Samples From Patients With Newly Diagnosed Pelvic Mass or Previously Diagnosed Ovarian Cancer

PRIMARY OBJECTIVES:

I. To evaluate the pre- and post-induction correlation between soluble folate receptor and
tumor-based receptor levels as a marker of malignancy in patients with newly diagnosed
adnexal masses. (Arm I) II. To evaluate the ability to induce serum folate receptor (FR)
with dexamethasone (Dex) and valproic acid (VPA) treatment in patients with newly diagnosed
adnexal masses. (Arm I) III. To evaluate the use of the serum soluble FR as a marker for
earlier detection of recurrent disease. (Arm II) IV. To evaluate the ability to induce FR
with Dex and VPA in the setting of recurrent disease. (Arm II)

SECONDARY OBJECTIVES:

I. To evaluate the expression of FR in primary versus (vs.) metastatic tumor sites in
patients with ovarian malignancy undergoing Dex and VPA induction and correlate expression
with other markers associated with malignancy (marker of proliferation Ki-67 [Ki67], cancer
antigen [CA]-125, etc.).

II. To analyze the correlation between gluco-corticoid receptor (GR) levels and serum FR
induction efficacy.

III. To examine global, downstream targets of GR and FR induction in patient samples
undergoing treatment with Dex and VPA.

OUTLINE: Patients are assigned to 1 of 2 arms.

ARM I (INDUCTION): Patients receive valproic acid orally (PO) twice daily (BID) on days -7
to -3 and once daily (QD) on day -2 and dexamethasone PO QD on days -5 and -2 and BID on
days -4 and -3. Patients undergo collection of serum and tissue samples for analysis via
polymerase chain reaction (PCR) and immunohistochemistry (IHC) at baseline, time of surgery,
and 7-14 days after surgery.

ARM II (SURVEILLANCE AND RECURRENCE): Patients receive valproic acid PO BID on days -7 to -3
and QD on day -2 and dexamethasone PO QD on days -5 and -2 and BID on days -4 and -3.
Patients undergo collection of serum and tissue samples for analysis via PCR and IHC at the
time of clinically suspected recurrence, 2 days after completion of induction, and 7-14 days
after induction.

Inclusion Criteria:

- For study Arm 1, female subjects of childbearing potential or less than 2 years
postmenopausal agree to use an acceptable form of contraception from the time of
signing informed consent until 30 days after study completion unless total
hysterectomy performed at the time of original operation

- Able to provide informed consent

- Performance status Eastern Cooperative Oncology Group (ECOG) 0-2

- Study Arm 1: primary diagnosis of a pelvic or adnexal mass of presumed gynecologic
origin who is scheduled for operative resection

- Study Arm 2: previously diagnosed with a non-mucinous epithelial ovarian carcinoma
(including serous, clear cell, and endometrioid histologies as well as borderline
ovarian tumors) currently undergoing routine surveillance for recurrence, having been
diagnosed with recurrence but prior to initiation of chemotherapy

Exclusion Criteria:

- Known sarcomatous histologies

- Current usage of VPA or Dex

- Any contraindication to dexamethasone or valproic acid such as known allergies or
sensitivity

- Unable to give informed consent

- Pregnancy

- Greater than 3 x the upper limit of normal (ULN) for alanine aminotransferase (ALT),
aspartate aminotransferase (AST)

- Greater than 3 x the ULN for total bilirubin (except for known cases of Gilbert's
syndrome, where the levels of conjugated bilirubin must be less than 3 x the ULN)

- Greater than 1.5 x the ULN for blood urea nitrogen (BUN)

- Greater than 1.5 x the ULN for creatinine

- Chronic or acute pancreatitis as evidenced by clinical or pathologic diagnosis

- Significant acute or chronic medical, neurologic, or psychiatric illness in the
subject that, in the judgment of the Investigator, could compromise subject safety,
limit the subject's ability to complete the study, and/or compromise the objectives
of the study

- For study Arm 2, patients that are currently undergoing chemotherapy for recurrence;
maintenance chemotherapy is not considered an exclusion criteria