Primary objectiveInvestigate if mMDSC/DC ratio in peripheral blood mononuclear cells (PBMCs) in patients with recurrent EOC before the start of treatment is associated with OS.See page 11 of the research protocol for secundary objectives.
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Association between the mMDSC/DC ratio in PBMCs in patients with recurrent EOC
before the start of treatment and OS.
Secondary outcome
* Association between the mMDSC/DC ratio in PBMCs in patients with recurrent
EOC before the start of treatment and PFS.
* Association between the mMDSC/DC ratio in PBMCs in patients with primary EOC
before the start of treatment and PFS/OS.
* Interaction between the mMDSC/DC ratio in PBMCs and EOC groups on PFS/OS.
* Association between mMDSC/DC ratio in PBMCs measured at different time points
in patients with primary and recurrent EOC and PFS/OS.
* Composition/counts and function of myeloid cells in PBMCs in patients with
primary and recurrent EOC before and during treatment and the association with
PFS/OS.
* Influence of the mMDSC/DC ratio and separate immune cell populations on the
tumor specific and general immune response.
* Determined, optimized and validated optimal cut-off point for the
macrophage/DC ratio and the mMDSC/DC ratio in PBMCs in patients with primary
and recurrent EOC for the different chemotherapeutic and immunotherapeutic
treatment modalities.
* Immune contexture of primary and recurrent tumors by determination of the
intratumoral immune subset numbers in fresh and archived tumor material and the
association with PFS/OS.
* Immune contexture of ascites by determination of the immune subset numbers in
ascites fluid of patients with primary and recurrent EOC and the association
with PFS/OS.
Background summary
Survival rates for patients with epithelial ovarian cancer, fallopian tube
cancer, and primary peritoneal cancer (EOC) are generally low and numerous
studies are currently exploring new, more efficient treatment strategies. EOC
is considered to be an immunogenic tumor. Therefore, new (experimental)
treatment strategies will focus on the combination of immunotherapy with other
therapies like chemotherapy. Two recent studies focussed on immunological
aspects of ovarian cancer treatment. Retrospective analyses in these patient
cohorts revealed two promising prognostic immune markers. The presence of high
numbers of macrophages, and especially monocytic myeloid cell derived
suppressor cells (mMDSCs), had a negative impact on overall survival (OS)
whereas a high level of dendritic cells (DCs) was associated with higher OS
after therapy. Importantly, the ratio of macrophages/DCs and in particular the
ratio of mMDSCs/DCs in blood samples of patients at baseline formed an
independent prognostic factor for OS after therapy. For each ratio an optimal
cut-off point was determined. However, these analyses were performed in a small
cohort and have not been validated in an independent cohort. Furthermore, it is
not clear whether the ratio of these cells in the circulation are a reflection
of the immune contexture within the tumor. Therefore, it is our aim to confirm
and validate our earlier observations and to study the immune contexture in
tumor tissue within a prospective cohort study of both recurrent and primary
EOC patients. These insights not only may help to define a prognostic biomarker
for patients with EOC but these ratio*s may also be predictive for the response
to immunotherapy since the cells involved are key to suppress or activate
tumor-specific T cell reactivity.
See also page 10 of the research protocol.
Study objective
Primary objective
Investigate if mMDSC/DC ratio in peripheral blood mononuclear cells (PBMCs) in
patients with recurrent EOC before the start of treatment is associated with OS.
See page 11 of the research protocol for secundary objectives.
Study design
A prospective, explorative cohort study.
Study burden and risks
This study involves the use of blood samples, which are obtained during routine
blood sampling. For the patients with (suspicion of) primary EOC, left over
tumor material and ascites, obtained during routine surgery, is used in this
study. Therefore, the burden and risk associated with participation of these
patients is considered very small. For the patients with recurrent EOC, two
extra biopsies (before and after systemic therapy) have to be obtained, which
can cause some discomfort and, although rarely, complications. Ascites fluid
will be collected only if there is an indication for ascites drainage.
Therefore, the burden and risk associated with participation of these patients
is considered limited. There are no direct benefits for participating patients.
Albinusdreef 2
Leiden 2333 ZA
NL
Albinusdreef 2
Leiden 2333 ZA
NL
Listed location countries
Age
Inclusion criteria
* Patients with (suspicion of) primary or recurrent EOC with an indication for
surgery, chemotherapy and/or immunotherapy.
* Age *18 years.
* WHO performance status 0-2.
* Accessible for treatment and follow-up.
* Written informed consent.
Exclusion criteria
* Other active malignancy in past 5 years prior to entry into the study, except
for treated non-melanoma skin cancer.
* Any known severe infection like HIV, hepatitis A, B and C.
* Receiving immune suppressive treatment.
* Medical or psychological condition which in the opinion of the investigator
would not permit the patient to complete the study or sign meaningful informed
consent.
Design
Recruitment
metc-ldd@lumc.nl
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 |
|---|---|
| ClinicalTrials.gov | NCTxVOLGT |
| CCMO | NL66869.058.19 |