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Ovarian Cancer Vaccine for Patients in Remission

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prima BioMed Ltd
ClinicalTrials.gov Identifier:
NCT01068509
First received: February 10, 2010
Last updated: June 23, 2016
Last verified: June 2016
  Purpose

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.

Condition Intervention Phase
Epithelial Ovarian Cancer
Biological: Cvac
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Prima BioMed Ltd:

Primary Outcome Measures:
  • Progression-free Survival [ Time Frame: Baseline to 48 weeks after the last visit or dose of Cvac (up to 104 weeks) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: Baseline to the end of the study (up to 4 years 10 months) ] [ Designated as safety issue: No ]
    Overall survival was defined as the time from randomization until death from any cause.

  • Change From Baseline in Mucin 1 Antibody Levels at Weeks 20, 56, and 104 [ Time Frame: Baseline to Week 104 ] [ Designated as safety issue: No ]
    Mucin 1 antibodies were assessed in serum samples using a quantitative enzyme-linked immunosorbent assay (ELISA). Detection was achieved with electrochemiluminescence.

  • 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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 63
Study Start Date: July 2010
Study Completion Date: April 2015
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01068509

Locations
United States, California
Marin Cancer Care, Inc.
Greenbrae, California, United States, 94904
Scripps Cancer Center
La Jolla, California, United States, 92037
Stanford University School of Medicine
Palo Alto, California, United States, 94305
University of California, San Francisco
San Francisco, California, United States, 94115
United States, Florida
Collaborative Research Group
Boca Raton, Florida, United States, 33487
United States, Georgia
Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Indiana
Indiana University Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, New Jersey
Morristown Medical Center
Morristown, New Jersey, United States, 07962
United States, New York
New York Downtown Hospital
New York, New York, United States, 10038
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Washington
University of Washington Medical Center
Seattle, Washington, United States, 98109
Australia, Queensland
Greenslopes Private Hospital
Greenslopes, Queensland, Australia, 4120
Gold Coast Hospital
Southport, Queensland, Australia, 4215
Australia, South Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia, 5000
Australia, Victoria
Peter MacCallum Cancer Cetnre
East Melbourne, Victoria, Australia, 3002
Austin Health Cancer Centre
Heidelberg, Victoria, Australia, 3084
Sponsors and Collaborators
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: James Mason, MD Scripps Cancer Center
Principal Investigator: Angeles Secord, MD Duke University
Principal Investigator: Peter Eisenberg, MD Marin Cancer Care
Principal Investigator: Giuseppe Del Priore, MD Indiana University Simon Cancer Center
Principal Investigator: Peter Rose, MD The Cleveland Clinic
Principal Investigator: Fernando Recio, MD Collaborative Research Group
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
  More Information

Publications:
Ozols RF, Rubin SC, Thomas G, et al. Epithelial ovarian cancer. In: Hoskins WJ, Perez CA, Young RC, eds. Principles and Practice of Gynecologic Oncology, 4th ed. Philadelphia: Lippincott Williams & Wilkins. 2005:919-922.
Desai J, Mitchell P, Loveland B, et al. A phase I trial of dendritic cells pulsed with MUC1 peptide in patients with solid tumours. Proc ASCO 2002; 21:15b (A1868).
Clinical Study Report: A Phase II Trial of Cellular Immunotherapy with M-FP Cancer Vaccine in Subjects with Epithelial Ovarian Cancer, 2007 (with permission from Martin Rogers of Prima Biomed).
Immunotherapy for Prostate AdenoCarcinoma Treatment (IMPACT) Phase 3 study summary of sipuleucel-T in castrate-resistant prostate cancer: http://www.bio-medicine.org/medicine-technology-1/
Austin Research Institute. SOP #811609. Leukapheresis for ex vivo Culture or Human Dendritic Cells for Immunotherapy. V004, 9 January 2004.
Austin Research Institute. SOP #8116 Stages 3-4. Procedures for the ex vivo Generation of MF-P Vaccine Pulsed SC, Phase I Clinical Trial. V006, 10 June 2003.

Responsible Party: Prima BioMed Ltd
ClinicalTrials.gov Identifier: NCT01068509     History of Changes
Other Study ID Numbers: CAN-003 
Study First Received: February 10, 2010
Results First Received: March 29, 2016
Last Updated: June 23, 2016
Health Authority: United States: Food and Drug Administration
Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council

Keywords provided by Prima BioMed Ltd:
Cvac

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on December 09, 2016