Back to resultsNEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer (NEODOC)
Primary Purpose
Epithelial Ovarian Cancer, Ovarian Carcinoma
Status
Recruiting
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
XP-DC vaccinations
Sponsored by
About this trial
This is an interventional treatment trial for Epithelial Ovarian Cancer focused on measuring immunotherapy, dendritic cell vaccination, ovarian cancer
Eligibility 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)
Sites / Locations
- Radboud University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
XP-DC vaccinations
Arm Description
Patients in this arm will receive XP-DC vaccination in addition to standard-of-care treatment.
Outcomes
Primary Outcome Measures
Number of patients with an immunological response to XP-DC vaccination
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
Safety as assessed by incidence of treatment-related adverse events
Toxicity will be assessed according to CTCAE version 4.03.
Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with stage III EOC
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.
Recurrence free survival (RFS) after 12 months
Number of patients with complete pathological response
Full Information
NCT ID
NCT05773859
First Posted
February 12, 2023
Last Updated
July 10, 2023
Sponsor
Radboud University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT05773859
Brief Title
NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer
Acronym
NEODOC
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 17, 2023 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Epithelial Ovarian Cancer, Ovarian Carcinoma
Keywords
immunotherapy, dendritic cell vaccination, ovarian cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
XP-DC vaccinations
Arm Type
Experimental
Arm Description
Patients in this arm will receive XP-DC vaccination in addition to standard-of-care treatment.
Intervention Type
Biological
Intervention Name(s)
XP-DC vaccinations
Other Intervention Name(s)
dendritic cell vaccine, cdc1
Intervention Description
Autologous cross-presenting dendritic cells loaded with autologous tumor lysate and KLH
Primary Outcome Measure Information:
Title
Number of patients with an immunological response to XP-DC vaccination
Description
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.
Time Frame
At DTH skin test after the second vaccination (approximately study week 10)
Secondary Outcome Measure Information:
Title
Safety as assessed by incidence of treatment-related adverse events
Description
Toxicity will be assessed according to CTCAE version 4.03.
Time Frame
Throughout the treatment phase until 1 year of follow-up
Title
Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with stage III EOC
Description
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.
Time Frame
Throughout the treatment phase until the last planned vaccination (approximately study week 23)
Title
Recurrence free survival (RFS) after 12 months
Time Frame
1 year
Title
Number of patients with complete pathological response
Time Frame
At time of debulking surgery (approximately study week 11)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Bouke Koeneman, MD
Phone
+31 (0)24 361 76 00
Email
bouke.koeneman@radboudumc.nl
Facility Information:
Facility Name
Radboud University Medical Center
City
Nijmegen
State/Province
Gelderland
ZIP/Postal Code
6500 HB
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bouke Koeneman, MD
Phone
+31243617600
Email
bouke.koeneman@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Nelleke Ottevanger, MD, PhD
Phone
+31243618800
Email
nelleke.ottevanger@radboudumc.nl
First Name & Middle Initial & Last Name & Degree
Jolanda de Vries, prof. dr.
First Name & Middle Initial & Last Name & Degree
Nelleke Ottevanger, dr.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer
We'll reach out to this number within 24 hrs