The main objective of the SOPI study is to select the HRD test that best predicts longest PFS on PARP-i in non-BRCA1/2 EOC patients, in order to adequately select patients that will benefit from a PARP-i. Secondary objectives are: to evaluate the 1-…
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
Progression Free Survival (PFS), defined as time from start PARP-i until
progression of disease or death from any cause, whichever comes first.
Secondary outcome
1 year and 3-year PFS, overall survival, grade 3-4 hematological toxicity or
grade >= 2 non-hematological toxicity leading to dose reduction or clinically
significant interruption (>2weeks) or stop PARP-i , time to subsequent therapy,
QoL and costs. We will collect blood and plasma samples during this research
(opt-in) to study whether we are able to identify ct-DNA and to examine whether
we are able to detect HRD using ct-DNA analysis. Some of the inclusion centers
use other genomic tests to diagnose BRCA1/2 in the tumor-first project (KWF
12732). We will compare the data of these tests with the HRD tests of the SOPI
study in an exploratory analysis. The Hartwig Medical Foundation will perform a
WGS of all ovarian cancer patients who are included in the SOPI study. We will
use and compare the WGS test with the results of our 3 tests.
Background summary
Epithelial ovarian cancer (EOC), including ovarian, tubal or peritoneal cancer,
is one of the most deadly cancers in women in the western world, with a 5-year
overall survival (OS) of 40%. The majority of patients present with advanced
disease, classified as FIGO stage III-IV. Standard of care consists of
debulking surgery and platinum based chemotherapy, and if applicable, a
maintenance therapy with a poly ADP-ribose polymerase (PARP)-inhibitor
(PARP-i). PARP-i have been shown to be highly effective for patients with a
germline or somatic BRCA1 or BRCA2 pathogenic variant, leading to improvements
in OS and progression free survival (PFS). However, for the majority of
patients, the benefit of PARP-i is less clear. Patients are selected for PARP-i
treatment based on disease characteristics and response to platinum based
chemotherapy. However, a reliable predictive test for clinical use is still
lacking. This leads to a part of the patients being exposed to highly costly
treatment with side effects without clinical benefit. Based on tumor biology,
only patients with a homologous recombination deficient (HRD) tumor will
benefit from PARP-i. Starting from January 1st 2024, only patients with a
positive HRD test are eligible for PARP-i. However, it is not clear which test
is the best in predicting HRD and which biomarker test predicts the best
response to PARP-i. Preliminary data analyzing HRD in breast cancer showed
around 30% discordance between three HRD tests. Direct comparison of HRD tests
in clinical trials will therefore be required to evaluate the optimal
predictive test for clinical decision making.
In the SOPI study we will evaluate three existing tests for identifying HRD
tumors in EOC patients and identify the test that best predicts sensitivity for
PARP-i. The societal impact of this project is considerable, since a reliable
HRD test that can identify patients that are likely to benefit from PARP-i will
reduce health care cost, protect patients from side effects and save time of
patients and health care providers.
Study objective
The main objective of the SOPI study is to select the HRD test that best
predicts longest PFS on PARP-i in non-BRCA1/2 EOC patients, in order to
adequately select patients that will benefit from a PARP-i.
Secondary objectives are: to evaluate the 1-year and 3-year PFS for the
non-BRCA1/2 mutant HRD group and the HRP group, defined according to each HRD
test, the overall survival, the best test strategy correlated with the longest
PFS in patients with advanced non-BRCA1/2 EOC treated with maintenance therapy
PARP-i, quality of Life (QoL) of patients (with HRD tumors) using PARP-i, and
cost-effectiveness for the three HRD tests.
Exploratory objectives are: to compare our tests to the Oncomine Comprehensive
Assay plus HRD tests performed in Leiden, the HRD IHKV tumor-first test
performed in Nijmegen and The WGS test performed by the Hartwig Medical
Foundation and to compare QoL of patients (with HRD tumors) using PARP-i with a
group of patients from the PlaComOv study that did not use PARP-i.
Study design
This is an observational multicenter study in advanced stage EOC patients who
will receive standard of care treatment with cytoreductive surgery (CRS) and
platinum-based chemotherapy. PARP-i treatment will also be given in a selected
group of patients as standard of care if applicable according to standard
European and national guidelines. In general, this includes patients with a
FIGO stage III-IV high grade serous/ endometrioid EOC with response to platinum
based chemotherapy and a BRCA1/2 pathogenic variant and/or a positive HRD test.
In the non-BRCA1/2 patients and we will compare the outcome of three HRD tests
and determine which test correlates best with PFS. QoL will be studied
throughout the study at predefined time points.
Study burden and risks
During regular procedures, tissue and blood samples will be collected,
minimizing any additional burden on the patient. Patients will receive
standardized QoL questionnaires pre-surgery, 4-6 weeks post-surgery, end of
primary treatment/ before start of PARP-i, after 6-months, and then yearly
post-surgery, until a maximum of 10 year after surgery. The time required to
complete the QoL questionnaire is approximately 15 minutes each time. No extra
hospital visits are planned for study procedures in the SOPI study.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
For biopsy:
- Women with suspected EOC, aged 18 years or older who give informed consent
for routine diagnostics including the sample for the HRD tests. In a
subpopulation we will compare HRD tests on tissue obtained at interval CRS as
well.
- Written informed consent
For Follow-up PARP-i:
- Patients with FIGO Stage III and IV EOC cancer who received standard of care
with debulking surgery and platinum based chemotherapy and are eligible for
PARP-i according to at least one positive HRD test.
- Patients with germline or somatic BRCA1/2 pathogenic variants in the tumor
will be asked to participate as (positive) controls
- Patients without BRCA1/2 pathogenic variant or HRD: only registration of PFS,
QOL and OS.
Control group:
- Included in the PlaComOv study (MEC-2017-500/NL62035.078.17) and given
informed consent for the use of data for future research.
Exclusion criteria
- Impossibility to obtain HRD test
- Other diagnosis than epithelial ovarian cancer
- Mucinous, low grade serous or clear cell type ovarian cancer
- Ineligibility for PARP-i treatment: such as (but not exclusive)
o Not reached at least partial response to neoadjuvant chemotherapy
o FIGO stage I-II disease
o All HRD tests negative and no BRCA 1/2 carrier
- Patients who are not able to understand/sign the Informed Consent.
- Known germline BRAC1/2 mutation
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 |
|---|---|
| CCMO | NL86420.078.24 |