Ovarian Cancer Vaccine for Patients in Remission

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

Official Title
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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

Conditions
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Epithelial Ovarian Cancer

Intervention / Treatment
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* Biological: Cvac


Participation Criteria
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Eligibility Criteria
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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.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-randomized Cvac<br>Participants received 6-8 intradermal injections of Cvac at 4 sites along both upper arms and both thighs. The 6-8 injections contained   60 × 10^6 dendritic cells. Following evaluation after the first dose, participants received additional injections as described for the randomized Cvac group below. | Biological: Cvac<br>* Cvac consists of autologous dendritic cells (DCs) incubated with the antigen, mannosylated fusion protein (M-FP), to target the DCs to the specific mucin 1 antigen.<br>|
| Experimental: Randomized Cvac<br>Participants received 6-8 intradermal injections of Cvac at 4 sites along both upper arms and both thighs every 4 weeks for 24 weeks (7 doses at Weeks 8, 12, 16, 20, 24, 28, and 32), and then every 8 weeks for 24 weeks (3 doses at Weeks 40, 48, and 56). The 6-8 injections contained   60 × 10^6 dendritic cells. | Biological: Cvac<br>* Cvac consists of autologous dendritic cells (DCs) incubated with the antigen, mannosylated fusion protein (M-FP), to target the DCs to the specific mucin 1 antigen.<br>|
| No Intervention: Observational standard of care<br>Participants in this group did not receive any treatment during the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was defined as the time from randomization to the date of documented disease progression or death from any cause, whichever occurred earlier. Disease progression occurred when a patient met either the Gynecologic Cancer Intergroup (GCIG) cancer-antigen (CA)-125 definition or the Response Evaluation Criteria in Solid Tumors (RECIST) radiological definition of progressive disease. The GCIG CA-125 definition of disease progression was defined as a CA-125 level ≥ 2 × the upper limit of normal documented on 2 occasions at least 1 week apart. The radiological RECIST criteria of disease progression was defined as the appearance of new lesions or an overall increase ≥ 20% or at least 5 mm in existing tumors. | Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from randomization until death from any cause. | Baseline to the end of the study (up to 4 years 10 months) | 
| Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 | Mucin 1 antibodies were assessed in serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). Detection was achieved with electrochemiluminescence. | Baseline to Week 104 | 
| Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104 | Intracellular cytokine staining (ICS) for IL2, IL4, IL17, tumor necrosis factor (TNF), and interferon gamma (IFNg) was done in both CD4+ and CD8+ cells from serum samples collected at Weeks, 20, 56, and 104. Intracellular cytokine staining data were acquired with 8-color flow cytometry on a BD LSR II flow cytometer and a high-throughput screening microplate reader. | Baseline to Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cvac