NCT07449481

A Phase II Clinical Study of Utidelone and Bevacizumab With or Without Etoposide in Patients With Brain Metastases From Malignant Solid Tumors

A Single-Arm, Open-Label, Phase II Clinical Study of Utidelone and Bevacizumab With or Without Etoposide in Patients With Brain Metastases From Malignant Solid Tumors

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Sponsor: Tianjin Medical University Cancer Institute and Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Brain metastasis represents one of the worst prognostic outcomes in advanced malignant tumors. Approximately 10% to 40% of patients with solid tumors develop brain metastases, a incidence rate significantly higher than that of primary malignant brain tumors. Over 80% of patients present with multiple brain metastases at diagnosis, often precluding surgical intervention. Brain metastases typically occur in the late stages of cancer. Patients have often received multiple prior therapies and developed resistance to first- and second-line drugs, leaving limited pharmacological options. The rapid growth of intracranial tumors poses an immediate threat to life. Consequently, radiotherapy and surgery currently form the cornerstone of clinical management for these patients. Thus, developing effective systemic therapies is an urgent and unmet medical need . Utidelone, a new-generation epothilone anticancer agent, has demonstrated good efficacy and safety. Previous studies indicate that utidelone achieves higher concentrations in most tissues, including the brain, compared to plasma, suggesting its ability to readily cross the blood-brain barrier . Furthermore, a Phase III clinical trial in metastatic breast cancer showed that utidelone in combination with capecitabine significantly improved the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) compared to capecitabine alone in patients previously treated with anthracyclines and taxanes . A separate Phase II study demonstrated that bevacizumab combined with carboplatin achieved a central nervous system objective response rate (CNS ORR) of 63%, with a median PFS of 5.62 months and a median OS of 14.1 months in breast cancer patients with brain metastases . Regarding safety, utidelone has a relatively low incidence of adverse reactions aside from peripheral neurotoxicity . Based on this evidence, this proposed study aims to evaluate the efficacy and safety of utidelone and bevacizumab, combined with etoposide for breast cancer cohorts or without etoposide for lung cancer cohorts, in patients with malignant tumor brain metastases.

Detailed description

Brain metastases from malignant tumors often occur in the advanced stages of the disease. Patients have typically undergone multiple treatments and developed resistance to first- and second-line drugs, leaving limited therapeutic options. Furthermore, the rapid growth of intracranial tumors is life-threatening. Therefore, the current mainstay of clinical treatment for patients with malignant brain metastases is radiotherapy and surgery. There is a significant unmet clinical need for systemic treatment options that offer short-term benefits and a low risk of inducing drug resistance. Utidelone, as a new-generation microtubule inhibitor, is not a substrate for P-glycoprotein, which contributes to its low potential for inducing resistance. Its small molecular size enables it to cross the blood-brain barrier. In clinical practice, it has shown good efficacy in patients with brain metastases. Bevacizumab is a humanized monoclonal antibody against vascular endothelial growth factor (VEGF) receptor. It exerts its effect by binding to VEGF, thereby blocking downstream signaling pathways, effectively inhibiting tumor growth with high specificity \[8\]. Studies have shown that administering Bevacizumab to glioma patients undergoing radiotherapy and chemotherapy can effectively improve immune function, enhance therapeutic efficacy, and prolong survival . A phase II clinical study led by Professor Shi Yehui from Tianjin Cancer Hospital explored the efficacy of a regimen combining Utidelone, Etoposide, and Bevacizumab in patients with HER2-negative breast cancer and brain metastases. Key data from this study were selected for poster presentation at ESMO 2023 and later for a Rapid Oral Abstract presentation at ASCO 2025, receiving recognition at international academic conferences. This confirms that the Utidelone-based combination regimen provides significant survival benefits for this patient population. Patient enrollment for this study has been completed, with some patients still under follow-up. Building on the breakthrough in treating breast cancer brain metastases, this research will further explore the clinical value of Utidelone-based combination regimens in patients with lung cancer brain metastases. Regarding other malignant tumors: Research directions and treatment plans for other cancer types will be determined after the completion of the breast and lung cancer studies and the assessment of their efficacy and safety. This study is a single-arm, multicenter, open-label, phase II clinical trial recruiting patients with lung cancer brain metastases. Eligible patients will receive treatment with a regimen combining Utidelone and Bevacizumab.

Conditions

• Malignant Solid Tumor
• Brain Metastasis

Interventions

Type	Name	Description
DRUG	Utidelone	Treatment Plan for Patients with Lung Cancer Brain Metastases: Utidelone Injection: 30 mg/m²/day by intravenous infusion, administered on Days 1 to 5, in a 21-day treatment cycle. Bevacizumab: 5-7.5 mg/kg, administered on Day 1, in a 21-day treatment cycle. Treatment Duration: The combination therapy should be administered for at least 4 to 6 cycles. If the patient achieves disease response or stability, the combination regimen may be continued. Treatment persists until disease progression (PD), unacceptable toxicity, or patient withdrawal occurs.
DRUG	Bevacizumab	Bevacizumab

Timeline

• Start date: 2026-05-01
• Primary completion: 2028-02-01
• Completion: 2030-02-01
• First posted: 2026-03-04
• Last updated: 2026-04-01