NEOadjuvant Dendritic Cell Vaccination for Ovarian Cancer

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Биопрепарат XP-DC vaccinations
  Autologous cross-presenting dendritic cells loaded with autologous tumor lysate and KLH

Первичные конечные точки

• Number of patients with an immunological response to XP-DC vaccination [Срок оценки: At DTH skin test after the second vaccination (approximately study week 10)]

Вторичные конечные точки (4)

• Safety as assessed by incidence of treatment-related adverse events [Срок оценки: Throughout the treatment phase until 1 year of follow-up]
• Feasibility of tumor lysate-loaded XP-DC vaccinations in patients with advanced EOC [Срок оценки: Throughout the treatment phase until the last planned vaccination (approximately study week 23)]
• Recurrence free survival (RFS) after 12 months [Срок оценки: 1 year]
• Number of patients with complete pathological response [Срок оценки: At time of debulking surgery (approximately study week 11)]

Критерии участия

Критерии включения

• 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 or low 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, 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

Критерии исключения

• Recurrent ovarian cancer
• Histologies other than high grade serous ovarian cancer such as, but not restricted to, endometrioid, 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Нидерланды · 1 центр

• Radboud University Medical Center — Nijmegen

Публикации

• Koeneman B, Schreibelt G, Duiveman-de Boer T, Bos K, van Oorschot T, Pots J, Scharenborg N, de Boer A, Hins-de Bree S, de Haas N, de Goede A, Westdorp H, van Ham M, de Vries IJM, Ottevanger PB. NEOadjuvant Dendritic cell therapy added to first line standard of care in advanced epithelial Ovarian Cancer (NEODOC): protocol of a first-in-human, exploratory, single-centre phase I/II trial in the Nethe PMID 41213670

Идентификаторы

NCT: NCT05773859 · NEODOC

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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