NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer (NEODOC)

Radboud University Medical Center

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Epithelial Ovarian Cancer

Ovarian Carcinoma

Treatments

Biological: XP-DC vaccinations

Study type

Interventional

Funder types

Other

Identifiers

NCT05773859

NEODOC

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 estimated patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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 IIIb, IIIc, IVa or IVb if only lymph nodes ≤ 1cm above the diaphragm or in the groins
Extensive abdominal spread of tumor
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:
- Amenorrhoeic for 1 year or more following cessation of exogenous hormonal treatments;
- or 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, IIIa or IVb with liver, spleen or lung metastases or lymph nodes above the diaphragm or in the groins > 1 cm
History of any second malignancy, with the exception of adequately treated basal cell carcinoma, cervical cancer > 5 years ago or early stage breast cancer >10 years ago.
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)