NEODOC: NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer

Sponsor

Radboud University Medical Center (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05773859

Collaborator

(none)

Enrollment

Location

Arm

19.1

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

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

Study Type:

Interventional

Anticipated 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

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Oct 1, 2024

Anticipated Study Completion Date :

Oct 1, 2024

Arms and Interventions

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

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

Primary Outcome Measures

Number of patients with an immunological response to XP-DC vaccination [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

Safety of tumor lysate-loaded XP-DC vaccinations in patients with stage III EOC [Throughout the treatment phase until 1 year of follow-up]
Toxicity will be assessed according to CTCAE version 4.03.
Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with stage III EOC [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.
Recurrence free survival (RFS) after 12 months [1 year]
Number of patients with complete pathological response [At time of debulking surgery (approximately study week 11)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)