To induce a vaccine specific immune response, hereby we hope to introduce the possibility of a new treatment to improve patient outcome and survival.
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Ovarian and fallopian tube disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess whether the RNA-LPX OC vaccine induces a vaccine-specific immune
response (systemic & local)
Secondary outcome
To assess the safety and tolerability of intravenous RNA-LPX OC vaccination in
combination with carboplatin and paclitaxel by monitoring and evaluation of
adverse events.
Background summary
Advanced stage serous ovarian cancer (OC) is the leading cause of death from
gynaecological malignancies with a 5-year survival of no more than 40%. Current
treatment (surgery and chemotherapy) is initially effective, but almost all
patients suffer from chemotherapy-resistant relapse. Moreover, despite
adjustment of chemotherapeutic schedules and the introduction of innovative
targeted drugs, survival and quality of life have barely improved. A promising
new approach that may improve outcome for these patients is immunotherapy. In
particular, immune checkpoint inhibition (CPI) therapy targeting e.g. PD-L1 or
PD-1 have improved patient survival rates across malignancies, with some
responses also observed in ovarian cancer patients. Nevertheless, response to
CPIs is almost always dependent on a pre-existing anti-cancer immune response,
frequently absent in ovarian cancer patients.
In order to increase/ induce an anti-tumor response an optimized liposomal
formulated RNA vaccine targeting tumor-associated antigens (TAA) is developed.
This vaccine protects RNA from degradation by plasma RNAses and shows an almost
100% targeted accumulation of RNA in the spleen suggesting a direct delivery to
dendritic cells. Here, we therefore propose to increase/induce an anti-tumor
immune response in patients with ovarian cancer while receiving neoadjuvant
chemotherapy by use of the RNA lipoplex (LPX) OC vaccine.
The simultaneous treatment with vaccinations and neoadjuvant chemotherapy
provides a tumor immune environment where immune defences are decreased.
Thereby enhancing the effectiveness of a vaccine induced immune response.
Making it a perfect setting for the induction of a tumor specific immune
response, with the ultimate aim of moving towards combination therapy of
chemotherapy/vaccination with checkpoint inhibition for these patients.
Study objective
To induce a vaccine specific immune response, hereby we hope to introduce the
possibility of a new treatment to improve patient outcome and survival.
Study design
A GMP-grade RNA vaccine targeting serous OC antigens will be used to induce a
systemic immune response and more importantly tumor accumulation of
vaccine-induced T cells. Patients with primary epithelial ovarian carcinoma
will receive eight vaccinations, in the same period they will receive three
cycles of neoadjuvant chemotherapy (standard treatment).
Data collected for analyzing vaccine-specific immune response (systemic and
local) is obtained before and after vaccinations by:
- Collection of PBMCs for immune monitoring by venous blood collection wil
occur before vaccination (120mL) and a leukapheresis is planned after final
vaccination.
- collection of tumor material by biopsy before vaccination and surgery after
vaccination (standard care).
We will need to include at least 10 patients to determine the primary outcome
(vaccine specific immune response)
Intervention
Intravenous administration of the vaccine (8 times)
Study burden and risks
Participating patients in this phase I trial have an active disease and might
experience a direct benefit from this study. The ultimately intended benefit is
to induce a specific anti-cancer immune response which leads to eradication of
the malignant lesions, to less invasive surgery and fewer complications. When
long-lasting immunity is induced, the immunotherapy may also prevent recurrence
of the disease.
For this study 14 hospital visits are required, including 2 overnight
hospitalizations. Visits will be scheduled at the same day as regular visits as
much as possible. Vaccination by means of intravenous injection is performed
eight times with additional venapunctures for biomonitoring. Initial clinical
data from naked RNA studies has demonstrated that a dosage of 100 ug total RNA
is safe and sufficient for induction of a potent immune response. In order to
minimize the amount of additional venapunctures they will be combined with
blood sample collections for standard treatment where possible. Additional
study procedures not included in standard patient care are: 1 leukapheresis and
1 image guided tumor biopsy.
Hanzeplein 1 Hanzeplein 1
Groningen 9713 GZ
NL
Hanzeplein 1 Hanzeplein 1
Groningen 9713 GZ
NL
Listed location countries
Age
Inclusion criteria
- Primary epithelial OC patients whom are treated with neoadjuvant
chemotherapy, carboplatin/paclitaxel, and subsequent surgery.
- Age * 18 years
- Signed informed consent in accordance with institutional and
regulatory guidelines
- Life expectancy * 5 months
- Adequate access of the tumor for image guided biopsy
- Adequate(according to the instiutional standards) hematology, liver
and kidney function to undergo chemotherapy with carboplatin and paclitaxel
Exclusion criteria
or any other systemic intercurrent disease or condition that might affect
the immunocompetence of the patient, or treatment with systemic highly
immunosuppressive therapy (e.g. transplant recipients or patients who
underwent a splenectomy)
- Use of systemic continuous corticosteroid therapy (e.g. prednisone i.v.
or p.o. > 7,5 mg / day).
- Neurological toxicity > grade 1 at screening
- History of a second malignancy except curatively treated low-stage
tumors with a histology that can be differentiated from the serous OC
type
- Pregnancy
- Participation in a trial with another investigational drug within 30 days
prior to the enrolment in this trial
- Any condition that in the opinion of the investigator could interfere
with the conduct of the trial.
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 |
|---|---|
| EudraCT | EUCTR2017-004585-10-NL |
| CCMO | NL62905.000.18 |