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

Study Overview
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Brief Summary
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To determine if a vaccine made from the patient's own tumor tissue can stimulate an immune response against the patient's tumor cells. To determine the safety of the vaccine.

Detailed Description
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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

Official Title
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OVax®: A Feasibility Study Using a DNP-Modified Autologous Ovarian Tumor Cell Vaccine as Therapy in Ovarian Cancer Patients After Relapse:

Conditions
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Adenocarcinoma of the Ovary

Intervention / Treatment
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* Biological: OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>5 million OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells | Biological: OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine<br>* OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months<br>* Other names: O-Vax;|
| Experimental: 2<br>2.5 million OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells | Biological: OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine<br>* OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months<br>* Other names: O-Vax;|
| Experimental: 3<br>0.5 million OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells | Biological: OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine<br>* OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months<br>* Other names: O-Vax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cell-mediated immunity to autologous tumor cells |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ovarian cancer, vaccine, immunotherapy, autologous