Trial Title:
Efficacy and Adverse Effects of Niraparib in Ovarian Cancer.
NCT ID:
NCT05583799
Condition:
Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Conditions: Keywords:
niraparib
efficacy and adverse effects
real word
prospective
product registration study
Study type:
Observational [Patient Registry]
Overall status:
Not yet recruiting
Study design:
Time perspective:
Prospective
Summary:
Ovarian cancer is the second fatal gynecological cancer. More than 70% of ovarian cancer
patients are diagnosed as advanced. Niraparib was approved by the National Medical
Products Administration on December 27, 2019. It can be used as a maintenance treatment
for adult patients with platinum-sensitive recurrent epithelial ovarian cancer, fallopian
tube cancer, or primary peritoneal cancer after platinum-containing chemotherapy has
achieved complete or partial remission. On September 10, 2020, niraparib became a poly
ADP-ribose polymerase inhibitor approved in China and globally, which can be used as a
single agent for the maintenance treatment of first-line and recurrent ovarian cancer
regardless of the patient's biomarker status. On December 28, 2020, niraparib has been
included in the new version of the medical insurance catalog. At present, most studies
based on niraparib are randomized controlled trials (RCTs). 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 v.1.1 criteria, we
evaluated the use of niraparib in patients with ovarian cancer, fallopian tube cancer, or
primary peritoneal cancer in the progression-free survival, overall survival, and
objective control rate, etc. The safety and tolerability of niraparib and the impact on
the quality of life of patients are evaluated. 10ml blood samples of enrolled patients
are collected at baseline and study endpoints respectively (only for enrolled patients
who agree to blood sampling) for exploratory biological marker research and exploratory
pharmacogenetic analysis. Finally, the results will as a supplement to the conclusions of
randomized controlled trials to provide better guidance for patients.
Detailed 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 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 (DSB) 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-ADP-ribose polymerase (PARP) 1 is a key ribozyme involved in
single-strand break repair through the base excision repair pathway. In the absence
of 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 PAPP inhibitors
used as therapeutic agents in BRCA1/BRCA2 carriers.
Niraparib was approved by the National Medical Products Administration on December
27, 2019. It can be used as a maintenance treatment for adult patients with
platinum-sensitive recurrent epithelial ovarian cancer, fallopian tube cancer, or
primary peritoneal cancer after platinum-containing chemotherapy has achieved
complete or partial remission. On September 10, 2020, niraparib became a PARP
inhibitor approved in China and globally, which can be used as a single agent for
the maintenance treatment of first-line and recurrent ovarian cancer regardless of
the patient's biomarker status. On December 28, 2020, niraparib has been included in
the new version of the medical insurance catalog. The results of the international
phase III clinical trial (NOVA) of niraparib showed that niraparib can prolong the
median progression-free survival of ovarian cancer patients regardless of whether
the patients have germline BRCA mutations. Among patients with gBRCA mutations, the
risk of disease progression was reduced by 73% and progression-free survival was
4-fold longer than in the placebo group (21 months vs. 5.5 months). In patients
without the gBRCA mutation, the risk of disease progression was reduced by 55% and
progression-free survival was more than 2-fold longer (9.3 months vs 3.9 months).
The PRIMA clinical study showed that niraparib, as single-agent maintenance therapy,
can significantly prolong the progression-free survival of first-line
platinum-responsive ovarian cancer patients. The risk of disease progression and
death was reduced by 38% across all treated patient populations. In BRCA-mutated,
HRD-positive, and HRD-negative patients, niraparib reduced the risk of disease
progression or death by 60%, 57%, and 32%, respectively. This study proves that
niraparib becomes the first PARP inhibitor that can significantly improve the
progression-free survival of patients regardless of biomarker status, which is
expected to change the treatment of ovarian cancer in China. Recently, the first
all-round, multicenter phase III clinical study in a Chinese population (NORA)
showed that in patients with gBRCA mutations, median progression-free survival (PFS)
was significantly longer with niraparib as second-line maintenance therapy, compared
with placebo (not reached vs. 5.5 months, HR: 0.22) and those without gBRCA mutation
at ESMO 2020(11.1 vs. 3.9 months, HR: 0.40). The QUADRA study shows that niraparib
has a substantial survival benefit in women treated for ovarian cancer, especially
in HRD-positive platinum-sensitive patients, including not only BRCA-mutated
patients but also the BRCA wild-type population.
The above-mentioned studies based on niraparib 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 environment. 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 research, there are only
retrospective studies on the use of niraparib in ovarian cancer at home and abroad,
and the results are consistent with their corresponding RCTs. There is a lack of
prospective real-world evidence with higher levels of evidence.
2. Study drugs
The drug name is niraparib Tosylate capsules. This product is a 100mg capsule.
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 PAPP inhibitors niraparib in patients with ovarian cancer,
fallopian tube cancer, or primary peritoneal cancer. According to the inclusion and
exclusion criteria, we collect various information about the target research
participants, 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, and objective response rate. Moreover, we
collect and analyze the adverse reactions of study participants after taking
niraparib. 10ml blood samples of enrolled patients are collected at baseline and
study endpoints respectively (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. 222 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) carbohydrate antigen 125 (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: computed tomography/magnetic
resonance 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 Response Evaluation Criteria In Solid
Tumors 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 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 version 5.0, 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 niraparib 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 niraparib is a marketed drug, so niraparib
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 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 names. 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 in 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
ranges. Categorical variables are described by absolute value and the proportion of
the total number of patients. Χ2 test is 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.
The log-Rank test was used to evaluate the survival difference between each group.
The 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 for 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 software (version 22.0).
9. Quality control and quality assurance
All research processes should establish standardized operating procedures.
Criteria for eligibility:
Study pop:
Patients with primary ovarian cancer, fallopian tube cancer, or peritoneal cancer
confirmed by histology
Sampling method:
Non-Probability Sample
Criteria:
Inclusion Criteria:
1. Patients with primary ovarian cancer, fallopian tube cancer, or peritoneal cancer
confirmed by histology.
2. Patients who are taking niraparib.
3. Age greater than or equal to 18 years old.
4. Patients should voluntarily participate in the trial and provide signed informed
consent.
Exclusion Criteria:
1.Patients who are not currently taking niraparib treatment.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
October 15, 2022
Completion date:
September 30, 2025
Lead sponsor:
Agency:
First Affiliated Hospital Xi'an Jiaotong University
Agency class:
Other
Source:
First Affiliated Hospital Xi'an Jiaotong University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05583799
