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

Adenocarcinoma of the Ovary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00660101
• Other study ID #: A/100/0501
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• First received: April 16, 2008
• Last updated: December 2, 2015
• Start date: June 2008
• Est. completion date: January 2016

Study information

• Verified date: December 2015
• Source: AVAX Technologies
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 34
• Est. completion date: January 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Ovary
• Neoplasms, Glandular and Epithelial
• Ovarian Neoplasms

Intervention

Biological:
• OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine
OVax: Autologous, DNP-Modified Ovarian Cancer Vaccine cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months

Locations

Country	Name	City	State
United States	Cancer Treatment Centers of America (ERMC)	Philadelphia	Pennsylvania
United States	Cancer Treatment Centers of America (CTCA-Southwestern)	Tulsa	Oklahoma
United States	Cancer Treatment Centers of America (CTCA-Midwestern)	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
AVAX Technologies

Country where clinical trial is conducted

United States, 

References & Publications (2)

Berd D, Sato T, Maguire HC Jr, Kairys J, Mastrangelo MJ. Immunopharmacologic analysis of an autologous, hapten-modified human melanoma vaccine. J Clin Oncol. 2004 Feb 1;22(3):403-15. Epub 2003 Dec 22. — View Citation

Dunton CJ, Carlson JA, King SA, Bloome E, Neufeld J, Berd D. Immunological and clinical effects of autologous hapten-modified vaccine in patients with advanced ovarian carcinoma., 19: Abstract 1828 ed 2000. p. 466a.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cell-mediated immunity to autologous tumor cells		3 months	No
Secondary	Safety		9 months	Yes

External Links

•   AVAX Technologies
•   Cancer Treatment Centers of America