Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT04699006 |
| Other study ID # |
XJTU1AF2020LSK-205 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 21, 2021 |
| Est. completion date |
January 1, 2026 |
Study information
| Verified date |
December 2022 |
| Source |
First Affiliated Hospital Xi'an Jiaotong University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Ovarian cancer is the second fatal gynecological cancer. More than 70% of ovarian cancer
patients are diagnosed as advanced. Olaparib is the first oral poly adenosine
diphosphate-ribose polymerase inhibitor (PAPPi) approved by the U.S. Drug Administration
(FDA) in December 2014. It can be used as a maintenance treatment for adult patients with
platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer, and primary
peritoneal cancer after platinum-containing chemotherapy has achieved complete or partial
remission. At present, most studies based on olaparib are randomized controlled trials
(RCTs). Because RCTs often have strict inclusion and exclusion criteria and they are
implemented in a highly standardized environment. Its internal validity is high, but the
research results may not be able to be extrapolated to practice. This study is a prospective
real world study. In this study, based on the modified Response Evaluation Criteria in Solid
Tumors (RECIST 1.1), we evaluate the use of olaparib in patients with ovarian cancer,
fallopian tube cancer, and primary peritoneal cancer in the progression-free survival (PFS),
overall survival (OS), and objective control rate (ORR), etc. At the same time, the safety
and tolerability of olaparib and the impact on the quality of life of patients are evaluated.
Finally, we analyze the results as a supplement to the conclusions of randomized controlled
trials to provide better guidance for patients.
Description:
1. Research status at domestic and foreign
Ovarian cancer is the second fatal gynecological cancer. More than 70% of ovarian cancer
patients are diagnosed as advanced. Standard treatments include optimal reduction
surgery and platinum/taxane chemotherapy. Epithelial ovarian cancer (EOC) is the most
common histological type of ovarian cancer, up to 20% of high-grade serous ovarian
cancer (HGSOC) shows germline and/or somatic mutations in the BRCA1/BRCA2 gene. BRCA1
and BRCA2 are tumor suppressor genes that play a central role in repairing DNA
double-strand breaks (DSBS) through homologous recombination (HR). Due to their
increased sensitivity to DNA damage reagents, they extend the survival period of BRCA1
and BRCA2 mutant EOCs, among which BRCA2 vectors have the best survival rate.
Poly-adenosine diphosphate-ribose polymerase 1 is a key ribozyme involved in
single-strand break (SSB) repair through the base excision repair pathway. In the
absence of poly adenosine diphosphate-ribose polymerase(PARP) activity, these lesions
are considered to have transformed into DSB. Cells lacking HR, such as BRCA mutant
cells, are extremely sensitive to PARP inhibition. This phenomenon called "synthetic
lethality" has led people to study poly adenosine diphosphate-ribose polymerase
inhibitors (PARPi) used as therapeutic agents in BRCA1/BRCA2 carriers.
Olaparib is the first oral PARPi approved in the United States in December 2014 for the
fourth-line treatment of advanced ovarian cancer with BRCA mutations. In the early
development of PARPi olaparib, studies have found that platinum sensitivity seems to be
related to a higher objective response rate between BRCA carriers and non-carriers.
Gelmon et al. designed a phase II randomized trial Study 19, which evaluated the
efficacy of olaparib and placebo as maintenance therapy in patients with
platinum-sensitive serous ovarian cancer recurrence. Compared with the placebo group,
the median progression-free survival (PFS) of the olaparib group was significantly
longer (8.4 months for the olaparib group and 4.8 months for the placebo group (HR=0.35;
[95) % credibility interval (CI) =0.25-0.49]; p<0.001). Post-hoc analysis showed that
among BRCA germline mutations (gBRCA) carriers, the improvement of PFS in the olaparib
group was greater (HR≤0.18; [95%CI=0.10-0.31]; p <0.0001). The SOLO2 study is a
randomized, controlled phase III randomized controlled trial, which further confirmed
the findings of patients with gBRCA mutations in Study 19. At present, based on the
latest National Comprehensive Cancer Network (NCCN) guidelines and guidelines for the
clinical application of PAPPi for ovarian cancer, the first-line recommends
PARPi+bevacizumab (Bev) maintenance therapy, and PARPi maintenance therapy is the
standard treatment for platinum-sensitive recurrent epithelial ovarian cancer.
The above-mentioned studies based on olaparib are mostly randomized controlled trials
(RCTs). Because RCTs often have strict inclusion and exclusion criteria, they are
carried out in a highly standardized environment, so that the research subjects have
good homogeneity. The validity is high, but the research results may not be able to be
extrapolated to practice. Therefore, it is necessary to evaluate the role of treatments
for advanced diseases in the real world. To provide better guidance for patients,
real-world evidence is needed to make up for the lack of randomized controlled trials.
At present, in real-world researches, there are only retrospective studies on the use of
olaparib in ovarian cancer at home and abroad, and the results are consistent with its
corresponding RCTs. There is a lack of prospective real-world evidence with higher
levels of evidence.
2. Study drugs
The drug name is olaparib tablets. This product is a film-coated tablet. 1)150mg: green
to green/gray, oval, biconvex tablets, with "OP150" engraved on one side and blank on
the other side. 2)100mg: yellow to dark yellow, oval, biconvex tablets, with "OP100"
engraved on one side and blank on the other side.
3. Research programs
3.1 Overall design
This study is a prospective real-world product registration study. It is an
observational study. The main research content is to evaluate the efficacy and adverse
reactions of PARPi olaparib in patients with ovarian cancer, fallopian tube cancer or
primary peritoneal cancer. According to the inclusion and exclusion criteria, we collect
various information of the target research participants, and organize the data and
perform statistical analysis under the guidance of epidemiologists and statistical
experts. The curative effect is evaluated by indicators such as PFS, overall survival
(OS), and objective response rate (ORR). Moreover, we collect and analyze the adverse
reactions of study participants after taking olaparib. 20ml blood samples and surgically
removed histological samples of enrolled patients are collected (only for enrolled
patients who agree to blood sampling) for exploratory biological marker research and
exploratory pharmacogenetic analysis.
3.2 Sample size
This research is an observational study. 245 study participants are expected to be
included.
3.3 Stratification factors
This research can set up different plans according to the following different
stratification factors and research purposes.1) Number of treatment lines: first-line
maintenance, second-line maintenance, back-line treatment, excess indications. 2)
BRCA1/2 mutation status: positive, negative. 3) Platinum sensitive status: platinum
sensitive, platinum resistant. 4) CA125 level, etc.
3.4 Treatment plan
This study is a non-interventional study that only collects data and does not interfere
with clinical treatment. The medication is administered according to clinical
instructions, guidelines and local treatment routines.
4. Research process
4.1 Subject informed
Patients should sign an informed consent form before the start of the study. The
researchers need to explain the contents of the informed consent to the subjects in
detail. After the candidate has fully read and understood the informed consent, if she
agrees to participate in the study, the subject should sign and date the informed
consent. Researchers also need to sign and date the informed consent form.
4.2 Interview on selection
Within 7 days of the subjects' enrollment, the investigator collected baseline data,
including: general information; medical history diagnosis; past tumor treatment history;
family history; whether it meets the admission criteria.
4.3 Interview during treatment and the last interview
After the subjects are enrolled, the investigator will conduct a visit every 12 weeks.
The data include:
- Efficacy evaluation: CT/MRI imaging examination and tumor marker CA125 examination
are required.
- Safety evaluation: whether there are adverse events (AE).
- At baseline, at the same time as the RECIST assessment time (once every 12 weeks)
until the objective radiation disease progression or the end of the study treatment
interview, a functional assessment of cancer treatment-ovarian cancer (FACT-O)
questionnaire survey.
5. Safety evaluation
5.1 Definition of Adverse Events
AE refers to all the adverse medical events that occur after the subject receives the
experimental drug. It can be manifested as symptoms and signs, diseases or abnormal
laboratory tests, but it may not be causally related to the experimental drug.
5.2 Severity of adverse events
During the study period, the severity of AEs will be classified according to Common
Terminology Criteria for Adverse Events (CTCAE) v5.0, and AE of grade ≥3 will be
collected.
5.3 Relationship with study drug
When judging the correlation between AEs and study drugs, the following factors should
be considered: 1) It is definitely related; 2) It may be related; 3) Possibly
irrelevant; 4) Definitely irrelevant; 5) Undecidable.
5.4 Adverse event records
All adverse events that occur from the subject's first use of olaparib to 4 weeks after
the last dose, including observed by the investigator, obtained by inquiries, and
spontaneously reported by the subject should be fully recorded.
Researchers need to continue to follow up all AEs until the event is cured, returns to
baseline, reaches a stable state, or no more information is available. The researcher
needs to monitor and record the outcome of the AE in the subject's source file. After
the study, there is no need to actively collect new AEs.
6. Drug management
This study is a real-world study, and olaparib is a marketed drug, so olaparib needs to
be purchased and used by patients according to the normal procedures in the hospital.
7. Data recording and monitoring
7.1 Data logging
This project uses table records. According to Good Clinical Practice (GCP) requirements,
in order to ensure patient privacy, patient names should not appear. All patients' names
should be filled with name codes, and the codes should be abbreviated in Chinese name.
The specific dosage and time of medication are unknown, and should be filled in unknown
rather than blank or missing items. The researcher should ensure that all data must be
consistent with the "inpatient medical record".
7.2 Data monitoring
During the test process, the research unit will review the completed test case data,
check whether the data is correct, complete and standardized, and assess the
traceability of all data.
8. Statistical analysis
8.1 Definition of statistical analysis data sets
The study includes cases that have received at least one trial drug and have a safety
evaluation into the primary and secondary endpoint analysis. Those who have not used a
trial drug or have no research data after being selected can be eliminated. Excluded
cases should be kept for future reference and no statistical analysis should be
performed.
8.2 Statistical analysis methods
The continuous variables in this study are described by median and interquartile range.
Categorical variables are described by absolute value and the proportion of the total
number of patients. Χ2 test are used for comparison between groups. The method of
survival analysis is used to statistically process the follow-up data. Kaplan-Meier
method is used to draw the survival curve of the follow-up subjects. Log-Rank test was
used to evaluate the survival difference between each group. Cox regression model was
used to analyze the influencing factors of the survival time of each group of follow-up
subjects. Candidate influencing factors with a significance level of 0.05 in the
univariate analysis were selected into the multivariate analysis. For all analyses, the
test level α=0.05, when p<0.05 is considered statistically significant. All analyses
were performed using Statistical Product and Service Solutions (SPSS) software (version
22.0).
9. Quality control and quality assurance
All research processes should establish standardized operating procedures.
