This study has been transitioned to CTIS with ID 2024-512353-24-01 check the CTIS register for the current data. The primary objective of this study is to show immunological efficacy of autologous tumor-lysate loaded XP-DC in epithelial ovarian…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of the study is the immune response enhanced or induced by
autologous tumor lysate-loaded XP-DC in epithelial ovarian
cancer patients.
Secondary outcome
Secondary endpoints are
- the safety and feasibility of tumor lysate-loaded XP-DC vaccinations. Safety
will be evaluated by adverse events, WHO/ECOG performance status, physical
examinations and laboratory tests. Toxicity will be assessed according to CTCAE
version 4.3;
- changes in the immunological landscape in tumor material and mutational
status after chemotherapy combined with vaccination with DC vaccines;
- clinical efficacy (number with pathological response to chemotherapy, number
with complete interval debulking, progression free survival, overall survival;
Background summary
Epithelial ovarian cancer (EOC) is the deadliest gynaecological 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
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, we showed that naturally circulating blood-derived dendritic cells
(nDC) are potent in inducing cytotoxic immune responses and tumor regression in
cancer patients. However, there is even a more specialized DC subset, referred
to as XP-DC or cDC1. XP-DC have shown their superiority in preclinical models
in inducing cytotoxic T cell responses to cancer after uptake of necrotic tumor
cell material, a phenomenon called cross priming. XP-DC are hypothesized to be
ideal to induce cytotoxic immune responses against the scarce neoantigens
present in EOC tumors. Since tumor lysates are the easiest source of
personalized neoantigens we propose to vaccinate EOC patients with XP-DC loaded
with autologous whole tumor lysate.
Study objective
This study has been transitioned to CTIS with ID 2024-512353-24-01 check the CTIS register for the current data.
The primary objective of this study is to show immunological efficacy of
autologous tumor-lysate loaded XP-DC in epithelial ovarian cancer
patients undergoing (neo-)adjuvant chemotherapy. The secondary objectives are
the safety and feasibility of autologous tumor lysate-loaded XP-DC
vaccinations, clinical efficacy (number with pathological response to
chemotherapy, number with complete interval debulking, number progression-free
survival and overall survival), changes in the immunological landscape and
mutational status after, chemotherapy combined with XP-DC vaccination.
Study design
This study is a single arm, single center, exploratory, phase I/II study.
Intervention
Patients are treated with standard (neo-)adjuvant chemotherapy and debulking
surgery. On day 14 of every 21 days cycle of chemotherapy (6 cycles in total),
autologous whole tumor lysate-loaded XP-DC will be administered.
Study burden and risks
Based on the experience with nDC inoculations in patients with melanoma,
prostate cancer and endometrial cancer, we expect that the XP-DC will be well
tolerated by EOC patients. Common and expected side effects of nDC vaccination
are usually mild and include flu-like symptoms and local reaction at injection
site, both not greater than Common Terminology Criteria for Adverse Events
(CTCAE) grade 2. The side effects are completely reversible within 24-48 hours.
Because of this the risk classification in relation to the chance of adverse
events and the severity of the expected adverse events is defined as being
negligible.
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
• Age over 18 years old
• 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
Exclusion criteria
• Recurrent ovarian cancer
• 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 or renders patient ineligible for combined
carboplatin-paclitaxel chemotherapies
• Active infection of Hepatitis B, C, HIV and syphilis or any other serious
active infection
• Known allergy to shell fish
• Auto immune disease (exception: vitiligo is permitted)
• Chronic treatment with systemic immunosuppressive drugs (i.e. more than 10 mg
prednisolone equivalent)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512353-24-01 |
| EudraCT | EUCTR2021-000714-42-NL |
| CCMO | NL75563.000.22 |