Ovarian Cancer Vaccine for Patients in Remission

A Randomized, Open-label Phase IIb Trial of Maintenance Therapy With a MUC1 Dendritic Cell Vaccine (Cvac™) for Epithelial Ovarian Cancer Patients in First or Second Remission

The purpose of this study is to determine the safety and efficacy of an investigational therapeutic agent (Cvac) in ovarian cancer patients in first or second remission and to determine its ability to prevent cancer from returning.

Study objectives

Primary objectives:

• To confirm the safety of administering Cvac in this population.
• To determine the effects of Cvac on progression-free survival (PFS).

Secondary objectives:

• To determine overall survival (OS) for ovarian cancer patients who receive Cvac after achieving remission in the first or second-line setting.
• Evaluation of host immunologic response to Cvac administration.

An initial cohort of 7 patients were treated with Cvac in an open-label phase to confirm the safety and consistency of manufacturing between Cvac drug product manufactured in the United States (US) and Australia. After the manufacturing characteristics of Cvac were confirmed to be consistent and each patient in the initial cohort had completed 1 injection cycle of Cvac with no serious or treatment-related Grade 3 or 4 adverse events (AEs), 56 patients were enrolled and randomized (1:1) to either Cvac or observational standard of care (OSC).

Inclusion Criteria:

• Female subjects ≥ 18 years old with histologically confirmed Stage III or IV epithelial ovarian, primary peritoneal or fallopian tube cancer who have previously undergone surgical cytoreduction and received first or second line conventional chemotherapy and are currently in complete remission (based on clinical and radiologic studies).
• Cancer antigen (CA)-125 ≤ upper limit of normal with a prior history of an elevated CA-125.
• Able and willing to undergo mononuclear cell collection.
• Not more than 12 weeks between enrollment and the last dose of chemotherapy that resulted in complete remission.
• No prior surgery to the peritoneum or pleural space within 28 days of enrollment, excluding removal of catheters used for chemotherapy administration.
• No prior treatment with an investigational product within 30 days of enrollment.
• Baseline electrocardiogram within normal limits or any abnormalities deemed not indicative of cardiac disease for which intervention is required.
• Serum creatinine ≤ 2 mg/dL.
• Serum aspartate aminotransferase or serum alanine aminotransferase ≤ 2.5x the upper limit of normal or serum total bilirubin ≤ 1.5x the upper limit of normal.
• White blood cell count ≥ 3.0 K/µL; absolute neutrophil count ≥ 1.5K/µL; hemoglobin ≥ 9.0 g/dL, and platelets ≥ 100,000/mm^3. (These complete blood count results are required for enrollment. It should be noted that complete blood count results, including monocyte count ≥ 0.2 × 10^9/L, will be needed prior to leukapheresis to determine if sufficient dendritic cells can be obtained for Cvac™ manufacture.)
• Life expectancy of at least 12 months.
• Eastern Cooperative Oncology Group Performance Status of 0-1.
• All toxicities from prior therapies, excluding alopecia, must have resolved to Common Terminology Criteria for Adverse Events Grade ≤ 1.
• Must be non-pregnant and, if of childbearing potential, must use adequate birth control (hormonal or barrier method of birth control or abstinence) for the duration of the study and for 3 months after study completion.
• Able to provide written informed consent.

Exclusion Criteria:

• Coexisting or other malignancies unless in complete remission for not less than 3 years. Does not include in situ carcinoma of the cervix or basal cell or squamous cell carcinoma of the skin for which no restrictions apply, assuming they have been adequately treated.
• Ovarian germ cell, sarcoma, or mixed Mullerian tumors.
• Prior cancer vaccine or cellular therapy.
• Active uncontrolled infections or any organ system toxicity ≥ Grade 2 by Common Terminology Criteria for Adverse Events criteria.
• Inability to provide informed consent or to comply with study-related procedures.
• Concurrent systemic treatment with steroids or other immunosuppressive agents.
• Diagnosed immunodeficiency and/or autoimmune disorders.
• Myocardial infarction in the past 6 months and/or clinically significant heart disease.
• Infection with human immunodeficient virus (HIV), hepatitis B or C virus.
• Pregnant or breastfeeding.
• Evidence or history of central nervous system metastases.
• Full dose anticoagulation therapy administered within 7 days of leukapheresis procedure.
• Hematopoietic growth factors administered within 14 days of enrollment.