Trial of Autologous, Hapten-Modified Vaccine, OVAX, in Patients With Relapsed Stage III or IV Ovarian Cancer

To study the toxicity, safety and DTH response of DNP-modified autologous ovarian tumor cell
vaccine and the DTH response to unmodified ovarian tumor cells in patients with relapsed
ovarian cancer:

- To determine the tolerability and toxicity of the treatment regimen

- To determine whether O-Vax induces a DTH response to autologous, DNP-modified ovarian
cancer cells

- To determine whether O-Vax induces a DTH response to autologous, unmodified ovarian
cancer cells

Study Population: Patients with recurrent epithelial ovarian cancer whose therapeutic tumor
surgery provides a mass which yields adequate tumor cells for vaccine preparation and
delayed-type hypersensitivity (DTH) testing

Study Design: A Phase I/IIa double-blind, three-dose, multi-center study

Investigational Product: O-Vax: DNP-modified autologous ovarian tumor cell vaccine

Dosage Form: Cell suspension

Route of Administration: Intradermal

Dosage and Treatment Schedule: Prior to enrollment in the study, one dose of 5 x 106
modified and one dose of 5 x 106 unmodified autologous ovarian cancer cells will be
administered, to establish a negative DTH response at baseline. Three dosing regimens will
be used: 5 x 105, 2.5 x 106, or 5 x 106 DNP-modified autologous ovarian tumor cells. An
initial dose of DNP-modified autologous ovarian tumor cells* followed by cyclophosphamide
then weekly doses of DNP-modified autologous ovarian tumor cells mixed with Bacillus of
Calmette and Guérin (BCG) for 6 weeks, and completed with one dose of DNP-modified
autologous ovarian tumor cells mixed with BCG as a 6 month booster if adequate cells

- count determined prior to aliquoting for cryopreservation

Endpoints: Treatment-emergent and related adverse events, serious adverse events, and Grade
3 and 4 laboratory abnormalities

Other Parameters:

- Delayed-type hypersensitivity skin reactions for assessing the induction of immune
responses to DNP-modified and unmodified autologous ovarian tumor cells

- CA-125 levels

- Survival

- Exploratory analysis incorporating in vitro analysis of lymphocytes separated from
patient blood samples

Duration of Treatment: Up to 6 months

Duration of Subject Participation in Study: Three months from the patient's last vaccine

Duration of Follow-up: Survival information will be collected via phone or visit on a
quarterly basis for each patient beginning 30 days after the last scheduled visit

Number of Subjects Required to Meet Protocol Objectives: 42 evaluable subjects

Number of Study Centers: 4-5

Number of Individual Blood Draws: 13 draws over nine months

Volume of Blood Drawn: 11 Draws of 30 mL/draw (total 360 mL) and two draws of 50mL in
heparinized tubes

Inclusion Criteria:

Screening Phase

- Stage III or IV adenocarcinoma of ovary

- Candidate for surgery to excise the tumor

- Signed informed consent for tumor acquisition

Treatment Phase

- At least 18 years of age

- Standard surgical debulking to maximum extent possible

- Adequate amount of tumor tissue obtained from surgical debulking to prepare a series
of vaccines and skin test materials.

- Administration of intraperitoneal chemotherapy following surgical debulking
Intraperitoneal drug to consist of a taxane (paclitaxel or docetaxel) Dose of taxane:
paclitaxel=60-75 mg/m2 / weekly x 4 or docetaxel = 25 mg/m2 - weekly x 4

- Vaccines and DTH materials pass lot release

- Minimum of 2 weeks and maximum of 6 weeks following last dose of intraperitoneal
chemotherapy

- Immunocompetent, as determined by anergy panel performed 1 week after last dose of
intraperitoneal chemotherapy (baseline PPD+ patients allowed)

- Expected survival of at least 6 months

- Karnofsky performance status ³ 80

- Signed informed consent for protocol participation

Exclusion Criteria:

- Alkaline phosphatase > 2.5 x ULN

- Total bilirubin > 2.0 mg/dL

- Creatinine > 2.0 mg/dL

- Hemoglobin < 10.0 g/dL

- WBC < 3,000 /mm3

- Platelet count < 100,000/mm3

- Major field radiotherapy within 6 months prior to participation in the study

- Brain metastases, unless successfully treated at least 6 months prior to entry

- Prior immunotherapy (interferons, tumor necrosis factor, other cytokines [e.g.,
interleukins], biological response modifiers, or monoclonal antibodies) within 4
weeks prior to participation in the study

- Prior splenectomy

- Concurrent use of systemic steroids (Note: Topical steroid therapies [applied to the
skin] are not contraindicated for participation in the study, provided these are not
applied to either arm. Inhaled aerosol steroids are not contraindicated for
participation in the study.)

- Concurrent use of immunosuppressive drugs

- Concurrent use of antitubercular drugs (isoniazid, rifampin, streptomycin)

- Other malignancy within 5 years except curatively treated non-melanomatous skin
cancer and curatively treated carcinoma in situ of the uterine cervix

- Concurrent autoimmune diseases, e.g., systemic lupus erythematosus, multiple
sclerosis or ankylosing spondylitis

- Concurrent medical condition that would preclude compliance or immunologic response
to study treatment

- Concurrent serious infection or other serious medical condition

- Receipt of any investigational medication within 4 weeks prior to participation in
the study

- Known gentamicin sensitivity

- Anergic, defined by the inability to make a DTH to at least one of the following:
candida, mumps, tetanus, trichophyton (based upon availability), or PPD

- Vaccine lot release failure