A Phase II Clinical Study to Evaluate the Efficacy and Safety of Flazoparib Combined With Temozolomide After the Completion of Standard Concurrent Chemoradiotherapy (CCRT) in Newly Diagnosed Glioblastoma

Overview

A Phase II clinical study is planned to evaluate the efficacy and safety of fluzoparib combined with temozolomide in newly diagnosed glioblastoma patients after completing standard concurrent chemoradiotherapy (CCRT), explore the effectiveness and safety of this regimen, and find a better treatment option for glioblastoma patients

Interventions

• Drug Fluzoparib with Temozolomide
  Fluzoparib: 100mg, po.bid. Q4W, d1-28, for a total of 6 cycles Temozolomide (TMZ): 150-200 mg/m2, po. Q4W, d1-5, for a total of 6 cycles If unacceptable toxicity occurs and a dose reduction is required, it is recommended to first reduce the dose from 100 mg (2 tablets) to 50 mg (1 tablet) twice a day. If further dose reduction is required, it is recommended to reduce the dose from 50 mg (1 tablet) twice a day to 50 mg (1 tablet) once a day. If it is still intolerable, the patient should withdr

Primary outcome measures

• OS [Time frame: Patients were assessed up to 36 months from enrollment to first death (whichever occurred first)]

Secondary outcome measures (2)

• PFS [Time frame: From enrollment to the first appearance of disease progression or date death from any cause,whichever came first,assessed up to 36 mounths]
• ORR [Time frame: From enrollment to initial efficacy evaluation ,assessed up to 6 months]

Eligibility criteria

Inclusion criteria

• 1.Signed informed consent form (ICF);

2\. Age ≥18 years old, <70 years old;

3\. Based on postoperative MRI, the total resection range is ≥80% compared with preoperative MRI (resection for the purpose of biopsy is not eligible);

4\. Patients newly diagnosed with primary glioblastoma by imaging or pathology, completed concurrent chemoradiotherapy (CCRT), and planned to receive adjuvant TMZ treatment;

5\. Appropriate hematological treatment and end-organ function within 14 days before randomization, defined by the following laboratory results:

• Absolute neutrophil count (ANC) ≥1.5×109/L;
• Platelet count ≥100×109/L;
• Hemoglobin ≥90 g/L;
• Total bilirubin ≤1.5 ×ULN;
• AST and ALT ≤3 × ULN;
• Alkaline phosphatase ≤2.5 × ULN;
• Serum albumin ≥25 g/L;
• Serum creatinine ≤133 μmol/L;
• PT and aPTT ≤ 1.5 × ULN; 6. Karnofsky score ≥ 60; 7. Expected survival > 12 weeks; 8. Women of childbearing age\*: must use highly effective contraceptive methods (resulting in a contraceptive failure rate of <1% per year) from the date of informed consent until at least 3 months after the last dose of the study drug fluzoparib/TMZ (whichever occurs later).

Men: agree to use contraceptive measures, defined as follows: For female partners of childbearing potential or pregnant female partners, men must use highly effective contraceptive methods from the date of informed consent until at least 3 months after the last dose of the study drug fluzoparib/TMZ (whichever occurs later).

\*Women are postmenopausal women who have not reached postmenopausal status (continuous amenorrhea for ≥ 12 months without a confirmed cause other than menopause) and have not undergone surgical sterilization (removal of the ovaries and/or uterus).

Exclusion criteria

• 1\. During the concurrent chemoradiotherapy phase, the total radiotherapy dose is >60Gy; 2. Multifocal glioma (≥3 lesions); 3. Patients with primary infratentorial glioblastoma; 4. Patients with leptomeningeal disease; 5. Patients with stable or no dose reduction of corticosteroids within 14 days of randomization; 6. Pregnancy, lactation or breastfeeding (need to breastfeed or breastfeed during the study);

• Women of childbearing age (including women who have undergone tubal ligation) must undergo a blood pregnancy test 7. Major cardiovascular disease, including New York Heart Association heart disease (grade 2 or higher), myocardial infarction within 3 months before randomization, unstable arrhythmia requiring treatment within the first 3 months, and/or newly diagnosed unstable angina; 8. Known clinically significant liver disease, including active viral, alcoholic or other hepatitis, cirrhosis, and hereditary liver disease; 9. Poorly controlled type 2 diabetes, defined as glycated hemoglobin ≥8% or fasting blood glucose ≥8.8 during the screening period mmol/L; 10. Major surgery (requiring general anesthesia) is expected during the study; 11. Any severe or uncontrollable systemic disease, including uncontrollable hypertension (defined as blood pressure still higher than 150/90 mmHg after effective antihypertensive treatment) and active bleeding disorders; 12. Any anticancer treatment after CCRT, whether experimental or approved, including chemotherapy, immunotherapy, gene therapy, cancer vaccine, cell therapy, cytokine/hormone therapy, and/or radiotherapy; 13. Persistent toxicity related to previous treatment (according to NCI CTCAE v5.0 toxicity level as > 1); according to the investigator's judgment, alopecia, sensory neuropathy ≤ 2, or other safety risk level ≤ 2 are eligible for inclusion; 14. Malignant tumors other than the study disease within 5 years before randomization, except for patients without risk of death or metastasis (adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer, localized prostate cancer or ductal carcinoma in situ); 15. During the screening period, patients have active viral infections that require systemic treatment:

• HIV antibody positive;
• Active hepatitis B: defined as HBsAg positive or HBcAb positive, and HBV DNA test result > 2000 IU/mL;
• Active hepatitis C: defined as HCV antibody positive and PCR test HCV RNA positive. However, subjects with positive serum anti-HCV and negative HCV RNA can also be included;
• Syphilis infection (positive Treponema pallidum specific antibody); 16. Patients who the investigator believes are not suitable for participation in the trial or will violate the protocol

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07047066 · GBM-Ⅱ-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗