NCT02692976

Brief Summary

Prostate cancer is the only type of cancer in which conventional dendritic cells (DC) treatment has a beneficial effect on the overall survival. In this study investigators aim to show immunologic efficacy of tumor-peptide loaded natural DC in metastatic castration-resistant prostate cancer patients (mCRPC). The immunomonitoring will include:

  1. 1.functional response and tetramer analysis of delayed-type hypersensitivity infiltrating lymphocytes against tumor peptides and
  2. 2.type I interferon (IFN) gene expression in peripheral blood mononuclear cells, and
  3. 3.proliferative, effector cytokine- and humoral responses to keyhole limpet hemocyanin, a immunogenic protein providing T cell help.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Sep 2015

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2015

Completed
29 days until next milestone

First Submitted

Initial submission to the registry

September 30, 2015

Completed
5 months until next milestone

First Posted

Study publicly available on registry

February 26, 2016

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2017

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 6, 2019

Completed
Last Updated

November 14, 2019

Status Verified

November 1, 2018

Enrollment Period

2 years

First QC Date

September 30, 2015

Last Update Submit

November 13, 2019

Conditions

Prostatic NeoplasmsImmunotherapyDendritic CellsVaccines

Keywords

Castration-resistant prostate cancerDendritic CellsImmunotherapyVaccines

Outcome Measures

Primary Outcomes (3)

  • The immunogenicity of tumor-peptide loaded natural blood dendritic cells (myeloid DC, plasmacytoid DC and the combination of mDC/pDC) in metastatic castration-resistant prostate cancer (mCRPC) patients

    a.functional response and tetramer analysis of delayed-type hypersensitivity infiltrating lymphocytes against tumor peptides.

    18 months

  • The immunogenicity of tumor-peptide loaded natural blood dendritic cells (myeloid DC, plasmacytoid DC and the combination of mDC/pDC) in metastatic castration-resistant prostate cancer (mCRPC) patients

    b.type I interferon (IFN) gene expression in peripheral blood mononuclear cells.

    18 months

  • The immunogenicity of tumor-peptide loaded natural blood dendritic cells (myeloid DC, plasmacytoid DC and the combination of mDC/pDC) in metastatic castration-resistant prostate cancer (mCRPC) patients

    c.proliferative, effector cytokine- and humoral responses to keyhole limpet hemocyanin, a immunogenic protein providing T cell help.

    18 months

Secondary Outcomes (14)

  • Treatment-related adverse events assessment by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    18 months

  • Quality of life measurement by EORTC-QLQ-C30

    18 months

  • Quality of life measurement by EORTC-QLQ-PR25

    18 months

  • Quality of life measurement by BDI (PC)

    18 months

  • Quality of life measurement by CIS20-R

    18 months

  • +9 more secondary outcomes

Study Arms (3)

Myeloid dendritic cells (mDC) vaccinations

EXPERIMENTAL

Patients will be vaccinated intranodally three times biweekly with mDC (5x 106 cells; n=7, arm A). DC will be loaded with major histocompatibility complex (MHC) class I binding peptides of tumor antigens and NY-ESO-1 and MUC1 PepTivator® which covers the complete antigen. DC will be stimulated with protamine/mRNA and loaded with keyhole limpet hemocyanin (KLH) as an immune control.

Biological: mDC vaccination

Plasmacytoid dendritic cells (pDC) vaccinations

EXPERIMENTAL

Patients will be vaccinated intranodally three times biweekly with pDC (3x 106 cells; n=7, arm B). DC will be loaded with MHC class I binding peptides of tumor antigens and NY-ESO-1 and MUC1 PepTivator® which covers the complete antigen. DC will be stimulated with protamine/mRNA.

Biological: pDC vaccination

mDC and pDC vaccinations

EXPERIMENTAL

Patients will be vaccinated intranodally three times biweekly with the combination of mDC and pDC (5x 106 mDC/ 3x 106 pDC; n=7, arm C). DC will be loaded with MHC class I binding peptides of tumor antigens and NY-ESO-1 and MUC1 PepTivator® which covers the complete antigen. DC will be stimulated with protamine/mRNA and loaded with KLH (mDC only) as an immune control.

Biological: mDC and pDC vaccination

Interventions

mDC vaccinationBIOLOGICAL

Intranodal mDC vaccination

Myeloid dendritic cells (mDC) vaccinations
pDC vaccinationBIOLOGICAL

Intranodal pDC vaccination

Plasmacytoid dendritic cells (pDC) vaccinations
mDC and pDC vaccinationBIOLOGICAL

Intranodal mDC/pDC vaccination

mDC and pDC vaccinations

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men ≥ 18 years of age and older with confirmed (histologically or cytologically) adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
  • Human leukocyte antigen (HLA)-A2.1 positive
  • Asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)
  • Metastatic castrate-resistant disease defined as one or more of the following criteria that occurred while the patient was on androgen deprivation therapy:
  • Prostate-specific antigen (PSA)-progression defined by Prostate Cancer Working Group 2 (PCWG2) criteria by a minimum of two rising PSA levels with an interval of ≥ 1 week between each determination
  • Progression of nodal metastases defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria or progression on successive magnetic resonance imaging lymphangiographies (MRLs)
  • Bone disease progression defined by two or more new lesions on bone scan as described in PCWG2 criteria
  • Maintenance of castrate circumstances:
  • Ongoing primary androgen deprivation therapy (Gonadotropin-Releasing hormone agonist or antagonist) or bilateral orchiectomy
  • Serum testosterone level ≤ 1.73 nmol/L (50 ng/dL) at screening visit
  • PSA value ≥ 2 ng/ml
  • Absence of visceral metastases, malignant ascites or pleural effusion
  • Clinical absence of brain metastases
  • Chemotherapy naive
  • Life expectancy ≥ 6 months
  • +8 more criteria

You may not qualify if:

  • Hypercalcemia
  • History of any second malignancy in the previous five years, with the exception of adequately treated basal cell carcinoma
  • Known allergy to shell fish
  • Heart failure (New York Heart Association class III/IV)
  • Serious active infections
  • Active hepatitis B, C or HIV infection
  • Active syphilis infection
  • Autoimmune diseases (exception: vitiligo is permitted)
  • Organ allografts
  • An uncontrolled co-morbidity, e.g. psychiatric or social conditions interfering which participation
  • Previous treatment with sipuleucel-T,PROSTVAC, GVAX, chemotherapy, ipilimumab or denosumab (previous treatment with abiraterone acetate, ketoconazole or enzalutamide is permitted)
  • Treatment with flutamide, bicalutamide, or nilutamide within four weeks of study enrollment
  • Prior radiotherapy within four weeks prior to planned vaccination or presence of treatment-related toxicity
  • Continued use of non-steroidal anti-inflammatory drugs
  • Concurrent use of systemic corticosteroids \> 10 mg daily prednisone equivalent
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, 6500 HB, Netherlands

Location

Related Publications (2)

  • Westdorp H, Creemers JHA, van Oort IM, Mehra N, Hins-de Bree SM, Figdor CG, Witjes JA, Schreibelt G, de Vries IJM, Gerritsen WR, Ottevanger PB. High Health-Related Quality of Life During Dendritic Cell Vaccination Therapy in Patients With Castration-Resistant Prostate Cancer. Front Oncol. 2020 Oct 26;10:536700. doi: 10.3389/fonc.2020.536700. eCollection 2020.

    PMID: 33194595DERIVED

  • Westdorp H, Creemers JHA, van Oort IM, Schreibelt G, Gorris MAJ, Mehra N, Simons M, de Goede AL, van Rossum MM, Croockewit AJ, Figdor CG, Witjes JA, Aarntzen EHJG, Mus RDM, Bruning M, Petry K, Gotthardt M, Barentsz JO, de Vries IJM, Gerritsen WR. Blood-derived dendritic cell vaccinations induce immune responses that correlate with clinical outcome in patients with chemo-naive castration-resistant prostate cancer. J Immunother Cancer. 2019 Nov 14;7(1):302. doi: 10.1186/s40425-019-0787-6.

    PMID: 31727154DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Study Officials

  • Winald R Gerritsen, MD PhD

    Radboudumc, dep of Medical Oncology

    PRINCIPAL INVESTIGATOR

  • Fred Witjes, MD PhD

    Radboudumc, dep of Urology

    PRINCIPAL INVESTIGATOR

  • Jolanda IM de Vries, PhD

    Radboudumc, dep of Tumor Immunology, laboratory study coordinator

    STUDY DIRECTOR

Study Design

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

Study Record Dates

First Submitted

September 30, 2015

First Posted

February 26, 2016

Study Start

September 1, 2015

Primary Completion

September 1, 2017

Study Completion

March 6, 2019

Last Updated

November 14, 2019

Record last verified: 2018-11

Data Sharing

IPD Sharing
Will share

Data will be shared after all clinical and immunological data collection and analysis in a scientific publication.

Locations

NL(1)