Clinical trial NCT01068509: Ovarian Cancer Vaccine for Patients in Remission
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Epithelial Ovarian Cancer
Keywords: Cvac
Lead sponsor: Prima BioMed Ltd
Sponsor class: INDUSTRY
First posted: 2010-02-15
Enrollment: 63
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free Survival
timeFrame: Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks)
Secondary outcomes:
measure: Overall Survival
timeFrame: Baseline to the end of the study (up to 4 years 10 months)
measure: Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104
timeFrame: Baseline to Week 104
measure: Change From Baseline in ICS of IL2, IL4, IL17, TNF, and IFNg in CD4+ and CD8+ Cells at Weeks 20, 56, and 104
timeFrame: Baseline to Week 104
Other outcomes:
Locations:
city: Greenbrae
country: United States
facility: Marin Cancer Care, Inc.
state: California
city: La Jolla
country: United States
facility: Scripps Cancer Center
state: California
city: Palo Alto
country: United States
facility: Stanford University School of Medicine
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boca Raton
country: United States
facility: Collaborative Research Group
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: New York
country: United States
facility: New York Downtown Hospital
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
city: Greenslopes
country: Australia
facility: Greenslopes Private Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Cetnre
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health Cancer Centre
state: Victoria
Study officials:
affiliation: University of Washington
name: Heidi Gray, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: New York Presbyterian Hospital
name: Mark Moradi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Jonathan Berek, MD, MMS
role: PRINCIPAL_INVESTIGATOR
affiliation: Morristown Medical Center
name: Nana Tchabo, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medical University of South Carolina
name: Jennifer Young, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Scripps Cancer Center
name: James Mason, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Angeles Secord, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Marin Cancer Care
name: Peter Eisenberg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Indiana University School of Medicine
name: Giuseppe Del Priore, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The Cleveland Clinic
name: Peter Rose, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Collaborative Research Group
name: Fernando Recio, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northside Hospital
name: Benedict Benigno, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, San Francisco
name: John Chan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Austin Health Cancer Care
name: Paul Mitchell, MB ChB
role: PRINCIPAL_INVESTIGATOR
affiliation: Peter MacCallum Cancer Centre, Australia
name: Linda Mileshkin, MBBS
role: PRINCIPAL_INVESTIGATOR
affiliation: Royal Adelaide Hospital
name: Margaret Davy, MBBS, CGO
role: PRINCIPAL_INVESTIGATOR
affiliation: Greenslopes Private Hospital
name: Jeffrey Goh, MBBS, FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: Gold Coast Hospital
name: Marco Matos, FRACP
role: PRINCIPAL_INVESTIGATOR
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