Ovarian Cancer Vaccine for Patients in Remission

NCT01068509 | Completed Phase 2 Results DMC

• 1 other identifier: CAN-003
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 18

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.

Conditions

Epithelial Ovarian Cancer

Keywords

Cvac

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Survival

  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

  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

  Baseline to Week 104

Study Arms (3)

Non-randomized Cvac

EXPERIMENTAL

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

Randomized Cvac

EXPERIMENTAL

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

Observational standard of care

NO INTERVENTION

Participants in this group did not receive any treatment during the study.

Interventions

Cvac BIOLOGICAL

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.

Non-randomized Cvac; Randomized Cvac

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prima BioMed Ltd: lead

Study Sites (18)

Marin Cancer Care, Inc.

Greenbrae, California, 94904, United States

Location

Scripps Cancer Center

La Jolla, California, 92037, United States

Location

Stanford University School of Medicine

Palo Alto, California, 94305, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Collaborative Research Group

Boca Raton, Florida, 33487, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

New York Downtown Hospital

New York, New York, 10038, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

University of Washington Medical Center

Seattle, Washington, 98109, United States

Location

Greenslopes Private Hospital

Greenslopes, Queensland, 4120, Australia

Location

Gold Coast Hospital

Southport, Queensland, 4215, Australia

Location

Royal Adelaide Hospital

Adelaide, South Australia, 5000, Australia

Location

Peter MacCallum Cancer Cetnre

East Melbourne, Victoria, 3002, Australia

Location

Austin Health Cancer Centre

Heidelberg, Victoria, 3084, Australia

Location

Related Publications (16)

• Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008. CA Cancer J Clin. 2008 Mar-Apr;58(2):71-96. doi: 10.3322/CA.2007.0010. Epub 2008 Feb 20.

  PMID: 18287387 BACKGROUND

• Grossi M, Quinn MA, Thursfield VJ, Francis PA, Rome RM, Planner RS, Giles GG. Ovarian cancer: patterns of care in Victoria during 1993-1995. Med J Aust. 2002 Jul 1;177(1):11-6. doi: 10.5694/j.1326-5377.2002.tb04616.x.

  PMID: 12088472 BACKGROUND

• 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.

  BACKGROUND

• Markman M, Liu PY, Wilczynski S, Monk B, Copeland LJ, Alvarez RD, Jiang C, Alberts D; Southwest Oncology Group; Gynecologic Oncology Group. Phase III randomized trial of 12 versus 3 months of maintenance paclitaxel in patients with advanced ovarian cancer after complete response to platinum and paclitaxel-based chemotherapy: a Southwest Oncology Group and Gynecologic Oncology Group trial. J Clin Oncol. 2003 Jul 1;21(13):2460-5. doi: 10.1200/JCO.2003.07.013.

  PMID: 12829663 BACKGROUND

• Apostolopoulos V, McKenzie IF. Cellular mucins: targets for immunotherapy. Crit Rev Immunol. 1994;14(3-4):293-309. doi: 10.1615/critrevimmunol.v14.i3-4.40.

  PMID: 7538768 BACKGROUND

• 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).

  BACKGROUND

• Rustin GJ, Nelstrop AE, Bentzen SM, Bond SJ, McClean P. Selection of active drugs for ovarian cancer based on CA-125 and standard response rates in phase II trials. J Clin Oncol. 2000 Apr;18(8):1733-9. doi: 10.1200/JCO.2000.18.8.1733.

  PMID: 10764434 BACKGROUND

• Apostolopoulos V, McKenzie IF, Pietersz GA. Breast cancer immunotherapy: current status and future prospects. Immunol Cell Biol. 1996 Oct;74(5):457-64. doi: 10.1038/icb.1996.76.

  PMID: 8912009 BACKGROUND

• Apostolopoulos V, Karanikas V, Haurum JS, McKenzie IF. Induction of HLA-A2-restricted CTLs to the mucin 1 human breast cancer antigen. J Immunol. 1997 Dec 1;159(11):5211-8.

  PMID: 9548459 BACKGROUND

• Meyer T, Rustin GJ. Role of tumour markers in monitoring epithelial ovarian cancer. Br J Cancer. 2000 May;82(9):1535-8. doi: 10.1054/bjoc.2000.1174.

  PMID: 10789720 BACKGROUND

• Liu PY, Alberts DS, Monk BJ, Brady M, Moon J, Markman M. An early signal of CA-125 progression for ovarian cancer patients receiving maintenance treatment after complete clinical response to primary therapy. J Clin Oncol. 2007 Aug 20;25(24):3615-20. doi: 10.1200/JCO.2006.09.4540.

  PMID: 17704410 BACKGROUND

• 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).

  BACKGROUND

• 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/

  BACKGROUND

• Austin Research Institute. SOP #811609. Leukapheresis for ex vivo Culture or Human Dendritic Cells for Immunotherapy. V004, 9 January 2004.

  BACKGROUND

• 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.

  BACKGROUND

• Gray HJ, Benigno B, Berek J, Chang J, Mason J, Mileshkin L, Mitchell P, Moradi M, Recio FO, Michener CM, Secord AA, Tchabo NE, Chan JK, Young J, Kohrt H, Gargosky SE, Goh JC. Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial. J Immunother Cancer. 2016 Jun 21;4:34. doi: 10.1186/s40425-016-0137-x. eCollection 2016.

  PMID: 27330807 DERIVED

Related Links

• Related Info from Sponsor's Web Site

MeSH Terms

Conditions

Carcinoma, Ovarian Epithelial

Interventions

CCV-AV protocol

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Ovarian Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Results Point of Contact

• Title: Marc Voigt
• Organization: PrimaBioMed, Ltd.

marc.voigt@primabiomed.com.au

49 173 6771602

Study Officials

• 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 School of Medicine

  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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2010
• First Posted: February 15, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: April 1, 2015
• Last Updated: May 11, 2017
• Results First Posted: August 4, 2016

Record last verified: 2016-06

Locations

US (13); AU (5)