Inclusion Criteria:
1. Voluntary participation and written informed consent;
2. The age was 18-70 years old, with no gender limit;
3. Supratentorial space occupying lesions were diagnosed as glioblastoma by pathology;
4. Patients received standard radiotherapy and temozolomide concurrent chemotherapy
after surgery, and the interval between the last radiotherapy and the last
radiotherapy was ≥ 4 weeks (pseudo progression should be excluded);
5. MRI confirmed that the tumor had definite recurrence. The diameter of the
enhancement focus was more than 1 cm and more than 2 layers (layer spacing was 5
mm), or the recurrence was confirmed by pathology after re biopsy or operation;
6. The recurrence site or other reasons can not be resected;
7. The methylation status of MGMT promoter had been detected or was willing to be
detected before enrollment;
8. According to recist1.1, there was at least one measurable lesion;
9. KPS score ≥ 60 points;
10. The tablets can be swallowed normally;
11. The expected survival time was more than 3 months;
12. Sufficient organs and bone marrow function. The definition is as follows.
1. Neutrophil count (ANC) ≥ 1500 / mm3 (1.5 ×109 / L);
2. Platelet count (PLT) ≥ 100000 / mm3 (100 × 109 / L);
3. Hemoglobin (HB) ≥ 9 g / dl (90 g / L);
4. Serum albumin ≥ 2.8 g / dl;
5. Serum creatinine ≤ 1.5 times the upper limit of normal value (ULN) or
creatinine clearance rate ≥ 60 ml / min;
6. Total bilirubin (TB) ≤ 1.5 × ULN, or total bilirubin (TB) > 1.5 × ULN, but
direct bilirubin (DBIL) ≤ 1 × ULN; patients with liver metastasis should be ≤ 2
× ULN;
7. The level of AST / SGOT or ALT / SGPT should be ≤ 2.5 × ULN and ≤ 5 × ULN in
patients with liver metastasis;
8. Left ventricular ejection fraction (LVEF) ≥ 50%, QTc < 450 ms in male and <
470ms in female;
13. The international normalized ratio (INR) of prothrombin time was ≤1.5 and activated
partial thromboplastin time (APTT) were ≤1.5 times the upper limit of normal value
in patients who had not received anticoagulant therapy. Patients receiving full dose
or parenteral anticoagulant therapy can enter the clinical trial as long as the
dosage of anticoagulant drugs is stable for at least 2 weeks before entering the
clinical study, and the results of coagulation test are within the limits of local
treatment;
14. Women of childbearing age should have negative pregnancy test (serum or urine)
within 7 days before enrollment, and voluntarily use appropriate contraceptive
methods during the observation period and within 8 weeks after the last
administration of the study drug; for men, it should be surgical sterilization or
agree to use appropriate contraceptive methods during the observation period and
within 8 weeks after the last administration of the study drug;
15. Good compliance, can cooperate with the study and follow-up according to the
requirements of the program.
Exclusion Criteria:
1. Patients had been treated with PARP inhibitors in the past;
2. Previous allergic history of temozolomide or fluzoparide, previous allergy to
dacarbazine, and allergic reaction to temozolomide or fluzoparide;
3. Patients had inherited galactose intolerance, lactase deficiency and glucose
galactose malabsorption;
4. The following treatments or drugs were received before the first study treatment:
1. Major surgery (biopsy is allowed due to diagnosis) or severe trauma within 4
weeks before the first use of the study drug;
2. Received strong CYP3A4 inducer or inhibitor within 2 weeks after the first use
of the study drug;
3. Previously vaccinated with anti-tumor vaccine; vaccinated with live attenuated
vaccine within 28 days before the first study drug treatment or within 60 days
after the end of study drug treatment;
5. Currently participating in other clinical studies, unless it is an observational
(non intervention) clinical study or an intervention in the follow-up of a new
clinical study; or has participated in any other drug clinical study within 4 weeks
before the first administration, or no more than 5 half-life from the last study
medication;
6. Except basal cell carcinoma or squamous cell carcinoma of skin, superficial bladder
cancer, carcinoma in situ of cervix, intraductal carcinoma in situ of breast and
papillary thyroid carcinoma which can be treated locally and have been cured in the
past 5 years or at the same time;
7. Advanced patients with symptoms, spread to the viscera, and at risk of
life-threatening complications in a short period of time (including patients with
uncontrollable large amount of exudate [chest, pericardium, abdominal cavity];
8. Fever of unknown origin > 38.5℃ occurred during the screening period / before the
first administration (according to the researcher's judgment, fever caused by tumor
can be included in the group);
9. Severe infection (CTCAE > Level 2) occurred within 4 weeks before the first use of
the study drug, such as severe pneumonia, bacteremia, infection complications, etc.
the baseline chest imaging examination revealed active pulmonary inflammation,
symptoms and signs of infection within 2 weeks before the first use of the study
drug, or the need for oral or intravenous antibiotic treatment (excluding
prophylactic use of antibiotics)；
10. Within 6 months before entering the study, the following conditions occurred:
myocardial infarction, severe / unstable angina pectoris, NYHA grade 2 or above
cardiac insufficiency and clinically significant supraventricular or ventricular
arrhythmias requiring clinical intervention; hypertension with poor drug control
(systolic blood pressure continuously increased ≥ 150mmhg or diastolic blood
pressure ≥ 100mmhg);
11. History of gastrointestinal bleeding or tendency of gastrointestinal bleeding in the
past 6 months, such as esophageal varices, local active ulcer lesions, fecal occult
blood≥(+) (gastroscopy is required when fecal occult blood is (+));
12. Unable to swallow the study drug, chronic diarrhea (including but not limited to
irritable bowel syndrome, Crohn's disease, ulcerative colitis), intestinal
obstruction and other factors affecting drug administration and absorption;
13. Urine protein ≥ + + + or 24-hour urine protein > 1.0g;
14. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell
transplantation or congenital immunodeficiency was known;
15. Patients with active pulmonary tuberculosis infection found through medical history
or CT examination, or patients with active pulmonary tuberculosis infection within
one year before enrollment, or patients with active pulmonary tuberculosis infection
history one year ago but without regular treatment;
16. Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome
(AIDS); untreated active hepatitis B (hepatitis B, defined as hepatitis B virus
surface antigen [HBsAg] positive test results, HBV-DNA ≥ 500 Hepatitis C was defined
as hepatitis C antibody [HCV AB] positive, HCV-RNA higher than the detection limit
of analysis method and abnormal liver function), or combined with hepatitis B and
hepatitis C co infection;
17. Patients had a clear history of neurological or mental disorders, including epilepsy
and dementia, and was known to have a history of psychotropic substance abuse,
alcoholism or drug abuse;
18. Patients who were considered unsuitable for the study.
