A Phase III Study of SYHA1813 for Recurrent or Progressive High-Grade Meningiomas

Official title

SYHA1813 vs Investigators' Choice Treatment in Patients With Recurrent or Progressive High-Grade Meningiomas: A Randomized, Controlled, Multicenter, Phase III Study

Overview

This is a randomized, controlled, open-label, multicenter, Phase III clinical study designed to compare the efficacy and safety of SYHA1813 versus treatment of investigators' choice in patients with recurrent or progressive high-grade meningioma not amenable to local therapy.

Detailed description

Approximately136 participants with recurrent or progressive high-grade meningioma who have received surgical resection and radiotherapy will be enrolled and randomized 1:1 to receive either SYHA1813 (experimental group) or investigators' choice (control group) treatment. The primary endpoint is progression-free survival (PFS) assessed by blinded Independent Review Committee (BIRC) using the Response Assessment in Neuro-Oncology Working Group (RANO criteria) for meningioma.

Interventions

• Drug SYHA1813
  SYHA1813 20mg QD
• Drug Investigator's Choice Treatment
  Investigator's Choice Treatment：bevacizumab, temozolomide or hydroxyurea

Primary outcome measures

• Progression-Free Survival (PFS) as Assessed by RANO Criteria and Evaluated by BIRC [Time frame: Up to approximately 4 years]

Secondary outcome measures (12)

• PFS as Assessed by RANO Criteria and Evaluated by investigators [Time frame: Up to approximately 4 years]
• Overall Survival (OS) [Time frame: Up to approximately 4 years]
• Overall Survival Rate at 12 Months (OS-12) [Time frame: Up to approximately 4 years]
• Progression Free Survival Rate at 6 Months (PFS-6) as Assessed by RANO Criteria [Time frame: Up to approximately 4 years]
• Objective Response Rate (ORR) as Assessed by RANO Criteria [Time frame: Up to approximately 4 years]
• Disease Control Rate (DCR) as Assessed by RANO Criteria [Time frame: Up to approximately 4 years]
• Frequency and severity of TEAEs and SAEs [Time frame: Up to approximately 4 years]
• Cmax of SYHA1813 [Time frame: Cycles 1, 2, 3]
• Tmax of SYHA1813 [Time frame: Cycles 1, 2, 3]
• AUClast of SYHA1813 [Time frame: Cycles 1, 2, 3]
• AUCinf of SYHA1813 [Time frame: Cycles 1, 2, 3]
• t1/2 of SYHA1813 [Time frame: Cycles 1, 2, 3]

Eligibility criteria

Inclusion criteria

• 1\. Aged >= 18 years.
• 2\. Histologically confirmed WHO grade II/III meningioma (WHO CNS 5th) that is progressive or recurrent.
• 3\. Individuals must have received surgery and radiation therapy.
• 4\. There is at least one measurable intracranial tumor lesion in the baseline period (RANO-meningioma).
• 5\. KPS≥60.
• 6\. The expected survival time is >=3 months.
• 7\. The organ function level and related laboratory indicators must meet requirement.
• 8\. Agree to use reliable and effective methods of contraception during the study treatment period and for at least 3 months after the last study treatment.

Exclusion criteria

• 1\. Individuals who are known to have severe allergic reaction to the study drug or any other ingredients/excipients in the formulation.
• 2\. Meets one of the following conditions: patients with brainstem involvement or extracranial metastasis; patients with severe brain herniation or at risk of brain herniation.
• 3\. History of other malignant tumors within 3 years or concurrent active malignant tumors.
• 4\. The toxic reactions of previous anti-tumor treatments have not yet recovered to ≤ Grade 1.
• 5\. Have used potent inhibitors or inducers of CYP3A4, CYP2C19 or CYP1A2 within the 14 days prior to randomization or are still requiring continued use of such agents.
• 6\. Individuals currently receiving warfarin or other oral anticoagulants (excluding those who use low-dose anticoagulants to maintain patency of central venous access or prevent deep vein thrombosis).
• 7\. Individuals who are unable to undergo enhanced MRI (such as those with pacemakers, metal dentures, claustrophobia, contrast agent allergies, etc.).
• 8\. Individuals with evidence or medical history of bleeding tendency within 2 months prior to randomization.
• 9\. Individuals with urine protein ≥ 2+, and 24-hour quantitative urine protein ≥ 1.0 g/24 h upon testing.
• 10\. History of acquired immunodeficiency syndrome or HIV antibody positivity in the past; Active hepatitis C; Active hepatitis B.
• 11\. Individuals with poorly healing wounds or ulcers, or fractures that require treatment or exhibit poor healing.
• 12\. Within 14 days prior to randomization, there were severe chronic or active infections (including tuberculosis infections) that required intravenous injection of antibacterial, antifungal or antiviral therapy.
• 13\. Individuals with cardiovascular and cerebrovascular diseases of significant clinical significance.
• 14\. Have undergone surgery of major vital organs within 28 days prior to randomization (excluding puncture biopsy).
• 15\. Individuals with swallowing difficulties or known medication absorption disorders.
• 16\. Pregnant or lactating women.
• 17\. Any other conditions that may interfere with the participant's adherence to study procedures, compromise the participant's best interests in participating in the study, or affect study results.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07613450 · SYHA1814-006

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗