Ovarian Cancer Vaccine for Patients in Remission

April 4, 2017 updated by: Prima BioMed Ltd

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Queensland
      • Greenslopes, Queensland, Australia, 4120
        • Greenslopes Private Hospital
      • Southport, Queensland, Australia, 4215
        • Gold Coast Hospital
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital
    • Victoria
      • East Melbourne, Victoria, Australia, 3002
        • Peter MacCallum Cancer Cetnre
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health Cancer Centre
  • United States
    • California
      • Greenbrae, California, United States, 94904
        • Marin Cancer Care, Inc.
      • La Jolla, California, United States, 92037
        • Scripps Cancer Center
      • Palo Alto, California, United States, 94305
        • Stanford University School of Medicine
      • San Francisco, California, United States, 94115
        • University of California, San Francisco
    • Florida
      • Boca Raton, Florida, United States, 33487
        • Collaborative Research Group
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Simon Cancer Center
    • New Jersey
      • Morristown, New Jersey, United States, 07962
        • Morristown Medical Center
    • New York
      • New York, New York, United States, 10038
        • New York Downtown Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic Foundation
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina
    • Washington
      • Seattle, Washington, United States, 98109
        • University of Washington Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Non-randomized Cvac
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
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.
Experimental: Randomized Cvac
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
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.
No Intervention: Observational standard of care
Participants in this group did not receive any treatment during the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival
Time Frame: Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks)
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
Time Frame: Baseline to the end of the study (up to 4 years 10 months)
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
Time Frame: Baseline to Week 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
Time Frame: Baseline to Week 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Prima BioMed Ltd

Investigators

  • Principal Investigator: Heidi Gray, MD, University of Washington
  • Principal Investigator: Mark Moradi, MD, New York Presbyterian Hospital
  • Principal Investigator: Jonathan Berek, MD, MMS, Stanford University
  • Principal Investigator: Nana Tchabo, MD, Morristown Medical Center
  • Principal Investigator: Jennifer Young, MD, Medical University of South Carolina
  • Principal Investigator: Benedict Benigno, MD, Northside Hospital
  • Principal Investigator: John Chan, MD, University of California, San Francisco
  • Principal Investigator: Paul Mitchell, MB ChB, Austin Health Cancer Care
  • Principal Investigator: Linda Mileshkin, MBBS, Peter MacCallum Cancer Centre, Australia
  • Principal Investigator: Margaret Davy, MBBS, CGO, Royal Adelaide Hospital
  • Principal Investigator: Jeffrey Goh, MBBS, FRACP, Greenslopes Private Hospital
  • Principal Investigator: Marco Matos, FRACP, Gold Coast Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2010

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

February 10, 2010

First Submitted That Met QC Criteria

February 11, 2010

First Posted (Estimate)

February 15, 2010

Study Record Updates

Last Update Posted (Actual)

May 11, 2017

Last Update Submitted That Met QC Criteria

April 4, 2017

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CAN-003

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Epithelial Ovarian Cancer

Clinical Trials on Cvac

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Gambia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe