| Eligibility |
Inclusion Criteria:
1. The patient voluntarily joined the study and signed the informed consent.
2. Female, 18-75 years (calculated on date of signing informed consent).
3. Participant has histologically confirmed diagnosis of high-grade predominantly serous
ovarian cancer, fallopian tube cancer, primary peritoneal cancer; =grade II ovarian
endometrioid adenocarcinoma.
- Mixed tumors: contain high-grade serous component or endometrioid components over
50%.
4. Disease progression greater than 6 months (184 days) after completion of their last
dose of platinum chemotherapy.
5. Prior treatment with =2 platinum-containing chemotherapy regimens and disease
remission (complete or partial response) at the end of the last platinum chemotherapy,
which lasted until study administration, must be randomized to enrollment and start
trial drug administration within 8 weeks from the last chemotherapy administration.
- Preoperative neoadjuvant chemotherapy and postoperative chemotherapy counted as 1
chemotherapy treatment regimen.
- The last chemotherapy must be a platinum-based chemotherapy regimen.
- Patient must have received at least 4 cycles of treatment for the last
platinum-based chemotherapy, during or after platinum-containing chemotherapy,
concurrent use of other investigational drugs and treatment other than endocrine
therapy drugs are not permitted.
- A detectable lesion or CA-125 =2 ×ULN is required before the last platinum
treatment.
- The imaging results showed CR or PR during the last platinum-containing regimen,
CA125 decreased to within the ULN or =90% from pre-treatment level during
treatment and CA125 remained <1xULN or did not increase by >10% in 7 days before
the first treatment.
- If no lesion is assessed prior to chemotherapy, CA125 should be alleviated to the
ULN during treatment and maintained at <1xULN for 7 days prior to the first
treatment.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. The duration of continuous PARPi treatment during the previous maintenance treatment
period was =6 months.
8. Participant has adequate organ function as defined in the following contents (Any
blood component or cell growth factor within 14 days prior to randomization is not
permitted)
- Absolute neutrophil count (ANC) =1.5×10^9/L
- Platelets =100×10^9/L
- Hemoglobin =9g/dL
- Serum albumin =3g/dL
- Total bilirubin =1.5 ×ULN
- AST and ALT =3 × ULN, and for patients with liver metastases, AST and ALT levels
=5× ULN
- Serum creatinine =1.5 × ULN.
9. Patients with potential fertility must have had a negative blood or urine pregnancy
test within 72 hours prior to the first dose, are not breastfeeding, and must agree to
use a medically approved contraceptive (e.g., intrauterine device, birth control pill
or condom) for the duration of the trial and for a period of 6 months after the last
administration of fluzoparib or 2 months after the last administration of apatinib,
whichever is longer.
Exclusion Criteria:
1. Prior malignancy unless curatively treated and disease-free for > 5 years prior to
study entry; Prior adequately treated non-melanoma skin cancer, in situ cancer of the
cervix or breast cancer without recurrence over 3 years allowed.
2. The expected survival is less than three months.
3. Participants with untreated central nervous system metastases
- patients who had previously received systemic, radical brain or meninges metastases
(radiotherapy or surgery), had been stable for at least 1 month on imaging, had
stopped systemic sex hormone therapy (dose >10mg/ day or other therapeutic hormones)
for more than 2 weeks, and had no clinical evidence could be included.
4. Not able to swallow pills normally, or have abnormal gastrointestinal function
affecting drug absorption as judged by the researcher.
5. Intestinal obstruction within 3 months.
6. The urine protein = ++ and 24-hour urine protein level > 1.0g.
7. Patients with clinical symptoms of cancer ascites, pleural effusion, who need to
drainage, or who have undergone ascites drainage within 2 months prior to the first
administration.
8. Uncontrolled heart clinical symptoms or diseases, such as :(1) NYHA 2 or more heart
failure, (2) Unstable angina pectoris, (3) myocardial infarction within 1 year, (4)
Ventricular arrhythmias requiring intervention, (5) QTc>470ms.
9. Abnormal coagulation function (INR > 1.5 or prothrombin time (PT) > ULN+4 seconds),
bleeding tendency or receiving thrombolytic therapy are allowed to receive low-dose
low-molecular weight heparin or oral aspirin preventive anticoagulant therapy during
the study.
10. Significant bleeding symptoms or clear bleeding tendency, such as gastrointestinal
bleeding, hemorrhagic gastric ulcer or vasculitis, etc., within the first 3 months of
the randomization. If fecal occultation blood is positive at baseline, gastroscopy
should be performed if still positive after reexamination.
11. Active ulcers, unhealed wounds or fractures.
12. Uncontrolled hypertension by antihypertensive medication (systolic blood pressure
=150mmHg or diastolic blood pressure =90mmHg).
13. Any bleeding event with grade 2 or higher in CTCAE 5.0 within 4 weeks prior
randomization.
14. Active infection or unexplained fever >38.5 degrees during screening or before first
treatment.
15. Participants with congenital or acquired immune deficiency (such as HIV infection), or
active hepatitis (hepatitis B reference: HBsAg positive, HBV DNA=500 IU/ml; Hepatitis
C reference: HCV antibody positive, HCV virus copy number > upper limit of normal).
16. Received radiotherapy, chemotherapy, hormone therapy, or molecular targeted therapy,
less than 4 weeks after the completion of the last dose or less than 5 drug half-lives
before the study for oral molecular targeted drug; adverse events caused by previous
treatment (except hair loss) and not recover to =1 degree (CTCAE 5.0).
17. Arteriovenous thrombosis events, such as cerebrovascular accident (including transient
ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and
pulmonary embolism, etc. occurred within 6 months.
18. History of hereditary or acquired bleeding or coagulation disorders (e.g., hemophilia,
coagulopathy, thrombocytopenia, etc.).
19. Need receive other systemic anti-tumor therapy during the study period.
20. According to the investigators' judgment the subjects had other factors that might
have led to the forced termination of the study.
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