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NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer (NEODOC)

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ClinicalTrials.gov Identifier: NCT05773859
Recruitment Status : Not yet recruiting
First Posted : March 17, 2023
Last Update Posted : March 17, 2023
Sponsor:
Information provided by (Responsible Party):
Radboud University Medical Center

Study Description
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Brief Summary:
This goal of this single arm, single center, exploratory phase I/II clinical trial is to learn more about the immunological efficacy, safety and feasibility of an autologous tumor lysate-loaded autologous XP-DC (cDC1)-based vaccine in patients with ovarian cancer.

Condition or disease Intervention/treatment Phase
Epithelial Ovarian Cancer Ovarian Carcinoma Biological: XP-DC vaccinations Phase 1 Phase 2

Detailed Description:

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Despite intensified treatment, 5-year overall survival rates only improved modestly over the last 20 years and remain low at around 30% for patients with advanced disease in the Netherlands. To this day, results from trials with the checkpoint inhibitors, that have revolutionized treatment in other cancer types, have been disappointing in EOC. Therefore, novel effective therapies are long awaited.

Recently, naturally circulating blood -derived dendritic cells (nDC) were shown to be potent in inducing cytotoxic immune responses and tumor regression in cancer patients. An even more specialized DC subset, referred to as cDC1 (conventional Dendritic Cells type 1) or XP-DC (specialized cross presenting DC) have shown their superiority in preclinical models. They are better at inducing cytotoxic T-cell responses against tumors after uptake of necrotic tumor cell material, a phenomenon called cross-presentation. This capability in cross-presentation makes XP-DC an ideal DC type in combination with tumor lysate-loading to induce immune responses against the scarce neoantigens present in EOC tumors.

The objective of this exploratory trial is to investigate the immunological efficacy as well as safety and feasibility of tumor-lysate loaded XP-DC in EOC patients undergoing (neo-)adjuvant chemotherapy. To this end 10 patients with stage III ovarian cancer will be included and offered a combined approach with DC vaccination in addition to standard-of-care chemotherapy and surgery. Extensive monitoring of the immune system throughout the course of the trial will be performed.

Study Design
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Study Type : Interventional
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Induction of Neo-Antigen Specific Cytotoxic T Cells by Autologous Tumor Lysate-loaded Specialized Cross-Presenting Dendritic Cells in Epithelial Ovarian Cancer Patients Treated With Neoadjuvant Chemotherapy, the NEODOC Study
Estimated Study Start Date : March 2023
Estimated Primary Completion Date : October 2024
Estimated Study Completion Date : October 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: XP-DC vaccinations
Patients in this arm will receive XP-DC vaccination in addition to standard-of-care treatment.
 Biological: XP-DC vaccinations
Autologous cross-presenting dendritic cells loaded with autologous tumor lysate and KLH
Other Names:
  • dendritic cell vaccine
  • cdc1


Outcome Measures
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Primary Outcome Measures :
  1. Number of patients with an immunological response to XP-DC vaccination [ Time Frame: At DTH skin test after the second vaccination (approximately study week 10) ]

    Immunologically responding patients are defined as:

    T cells isolated from vaccine challenged sites (DTH biopsies) that can be expanded and 1) express T cell receptors specific for the vaccine and 2) show effector functions measured by IFN-gamma secretion or cytolytic activity against tumor antigen expressing target cells.

    Immunologically non-responding patients are defined as:

    No T cells, or T cells isolated from DTH biopsies that cannot be expanded, or T cells that can be expanded but do not recognize tumor antigens, or can recognize tumor antigens but do not display T effector functions i.e. lysis of tumor cell targets or release of IFN-α.



Secondary Outcome Measures :
  1. Safety of tumor lysate-loaded XP-DC vaccinations in patients with stage III EOC [ Time Frame: Throughout the treatment phase until 1 year of follow-up ]
    Toxicity will be assessed according to CTCAE version 4.03.

  2. Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with stage III EOC [ Time Frame: Throughout the treatment phase until the last planned vaccination (approximately study week 23) ]

    Feasibility assessment will be based on reporting of:

    • the number of patients from whom a successful apheresis product can be obtained
    • the number of patients from whom (both quantitatively and qualitatively) sufficient tumor lysate can be obtained
    • the number of patients for whom a DC product can be manufactured that meets the prespecified criteria
    • the number of patients that has received the planned number of vaccinations.

  3. Recurrence free survival (RFS) after 12 months [ Time Frame: 1 year ]
  4. Number of patients with complete pathological response [ Time Frame: At time of debulking surgery (approximately study week 11) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Women over 18 years old with histologically confirmed primary epithelial ovarian cancer.
  • Not amenable by primary debulking surgery and in need of neoadjuvant chemotherapy and interval debulking
  • High-grade serous histology
  • FIGO stage IIIc or FIGO stage IIIb with extensive abdominal spread
  • WHO/ECOG performance status 0-1
  • Neutrophils >1.5x 109/L lymphocytes >0.8x 109/L, platelets >100x 109/L, hemoglobin >5,6 mmol/L (9.0 g/dl), estimated glomerular filtration rate > 45 ml/min/1.73m2, AST/ALT <3 x ULN, serum bilirubin <1.5 x ULN (exception: Gilbert's syndrome is permitted)
  • Expected adequacy of follow-up
  • Postmenopausal or evidence of non-childbearing status or for women of childbearing potential: negative urine or serum pregnancy test, within 28 days of study treatment and confirmed prior to treatment on day 1. Postmenopausal is defined as 1) Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments or 2) surgical sterilisation (bilateral oophorectomy or hysterectomy).
  • Informed consent

Exclusion Criteria:

  • Recurrent ovarian cancer
  • Histologies other than high grade serous ovarian cancer such as, but not restricted to, endometrioid, low-grade serous, mucinous, clear cell or carcinosarcoma
  • Unable and/or unwilling to undergo standard chemotherapy and interval debulking surgery
  • FIGO stage I-IIb, stage IIIa, stage IV
  • History of any second malignancy, with the exception of adequately treated basal cell carcinoma
  • Any serious clinical condition that may interfere with the safe administration of DC vaccinations
  • Heart failure (NYHA class III/IV)
  • Any uncontrolled co-morbidity, e.g. psychiatric or social conditions interfering which participation
  • Unable to undergo a tumor biopsy
  • Pregnancy or insufficient anti-conception if reproduction is still possible
  • Active infection of Hepatitis B, C, HIV and syphilis
  • Serious other active infections
  • Known allergy to shell fish
  • Auto immune disease (exception: vitiligo is permitted)
  • History of organ allografts
  • Chronic treatment with systemic immunosuppressive drugs (i.e. more than 10 mg prednisolone equivalent)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05773859


Contacts
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Contact: Bouke Koeneman, MD +31 (0)24 361 76 00 bouke.koeneman@radboudumc.nl

Locations
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Netherlands
Radboud University Medical Center
Nijmegen, Gelderland, Netherlands, 6500 HB
Contact: Bouke Koeneman, MD    +31243617600    bouke.koeneman@radboudumc.nl   
Contact: Nelleke Ottevanger, MD, PhD    +31243618800    nelleke.ottevanger@radboudumc.nl   
Principal Investigator: Jolanda de Vries, prof. dr.         
Principal Investigator: Nelleke Ottevanger, dr.         
Sponsors and Collaborators
Radboud University Medical Center
More Information
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Responsible Party: Radboud University Medical Center
ClinicalTrials.gov Identifier: NCT05773859    
Other Study ID Numbers: NEODOC
First Posted: March 17, 2023    Key Record Dates
Last Update Posted: March 17, 2023
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Radboud University Medical Center:
immunotherapy
dendritic cell vaccination
ovarian cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
 Endocrine System Diseases
Gonadal Disorders
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vaccines
Immunologic Factors
Physiological Effects of Drugs