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

NCT07449481 | Not Yet Recruiting Phase 2

• 1 other identifier: E20251327
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Malignant Solid Tumor; Brain Metastasis

Keywords

NSCLC; SCLC; brain metastases

Outcome Measures

Primary Outcomes (1)

• CNS-ORR

  The best efficacy evaluation observed during the entire process from enrollment to the assessment of all central nervous system target lesions according to the RANO-BM criteria was the proportion of patients who achieved complete response (CR) and partial response (PR) among the total number of evaluable patients.

  Primary outcomes assessed from baseline until the end of study, up to 48 months.

Secondary Outcomes (8)

• CNS-CBR

  Secondary outcomes assessed from baseline until the end of study, up to 48 months.

• ORR

  Secondary outcomes assessed from baseline until the end of study, up to 48 months.From February 2026 to February 2030

• CNS-PFS

  Secondary outcomes assessed from baseline until the end of study, up to 48 months.

• PFS

  Secondary outcomes assessed from baseline until the end of study, up to 48 months.From February 2026 to February 2030

• Extracranial Objective Response Rate (EC-ORR)

  Secondary outcomes assessed from baseline until the end of study, up to 48 months.From February 2026 to February 2030

Study Arms (2)

Non-Small Cell Lung Cancer Cohort

EXPERIMENTAL

Patients with histologically confirmed non-small cell lung cancer (NSCLC) and brain metastases treated with Utidelone in combination with Bevacizumab. 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: Utidelone; Drug: Bevacizumab

Small Cell Lung Cancer brain metastasis Cohort

EXPERIMENTAL

Patients with histologically confirmed small cell lung cancer and brain metastases treated with Utidelone in combination with Bevacizumab。 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: Utidelone; Drug: Bevacizumab

Interventions

Utidelone DRUG

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.

Also known as: Bevacizumab

Non-Small Cell Lung Cancer Cohort; Small Cell Lung Cancer brain metastasis Cohort

Bevacizumab DRUG

Bevacizumab

Non-Small Cell Lung Cancer Cohort; Small Cell Lung Cancer brain metastasis Cohort

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must provide informed consent for the trial and voluntarily sign the written informed consent form (ICF) prior to the study.
• Aged 18-75 years, male or female.
• Patients with histologically or cytologically confirmed non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC):The pathological type of NSCLC must be adenocarcinoma.For advanced NSCLC patients with positive EGFR sensitive mutations, ALK fusion, ROS1 fusion, RET fusion, BRAF V600E, or NTRK fusion mutations, they must have experienced disease progression after adequate targeted therapy for the corresponding mutation AND after at least one platinum-based chemotherapy regimen, or be intolerant to platinum-based therapy.Patients with NSCLC without driver gene mutations and patients with SCLC must have experienced disease progression after platinum-based chemotherapy with or without PD-1/PD-L1 inhibitors, or be intolerant to the aforementioned therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0-2.
• At least one measurable lesion in the central nervous system (CNS).
• Patients who have not received chemotherapy, radiotherapy, surgical treatment, targeted therapy, or immunotherapy within 4 weeks prior to enrollment.
• All toxicities related to prior anti-tumor treatment must have recovered to ≤ Grade 1 (CTCAE v5.0), except for alopecia of any grade, which is permitted.
• CNS patients, based on screening brain Magnetic Resonance Imaging (MRI), must meet one of the following conditions:Untreated brain metastases not requiring immediate local therapy；Previously treated brain metastases, assessed by the investigator as having progressed after prior local CNS therapy and without clinical manifestations requiring immediate local therapy.
• Routine blood tests within 1 week prior to enrollment are essentially normal (based on the normal ranges of each research center's laboratory):
• White blood cell count (WBC) ≥ 3.0 × 10\^9/L；
• Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L；
• Platelet count (PLT) ≥ 100 × 10\^9/L；
• Hemoglobin ≥ 9.0 g/dL (Patients may receive blood transfusion or erythropoietin treatment to meet this criterion.)；
• Liver and kidney function tests within 1 week prior to enrollment are essentially normal (based on the normal ranges of each research center's laboratory):
• Total bilirubin (TBIL) ≤ 1.5 × Upper Limit of Normal (ULN)；

You may not qualify if:

• History of other malignancies (including primary brain or leptomeningeal tumors) within the past 5 years, except for cured basal cell skin carcinoma or cervical carcinoma in situ.
• Prior use of Utidelone injection or Bevacizumab.
• Imaging shows tumor invasion of major blood vessels, unclear demarcation from vessels, or judged by the investigator as having a high probability of fatal massive hemorrhage due to tumor invasion of important vessels during the study (major thoracic vessels include the thoracic aorta, left pulmonary artery, right pulmonary artery, 4 pulmonary veins, superior vena cava, inferior vena cava, and aorta).
• Major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the first dose of study drug, or scheduled elective surgery during the trial period.
• History of Grade 3 or higher severe neurological adverse reactions related to prior anti-microtubule drug use.
• Any untreated brain lesion \> 2.0 cm, unless discussed and approved for enrollment by the investigator.
• Ongoing use of systemic corticosteroids to control brain metastasis symptoms, with a total daily dose \> 2 mg dexamethasone (or equivalent). However, a chronic stable dose ≤ 2 mg dexamethasone daily (or equivalent) may be permitted after discussion and approval by the investigator.
• More than 2 episodes of seizures within 4 weeks prior to enrollment.
• Poorly controlled hypertension, or history of hypertensive crisis or hypertensive encephalopathy.
• History of hemoptysis within 6 months prior to enrollment, or evidence of bleeding tendency or significant coagulation dysfunction within the past month.
• Current use of full-dose warfarin or equivalent agents, or use of aspirin (325 mg/day) within 10 days.
• Major surgery, open biopsy, or significant traumatic injury within 28 days, or anticipated need for such during the study.
• Severe gastrointestinal toxicity prior to the first dose of study drug that has not recovered to below Grade 2; or confirmed presence of other clinically uncontrolled acute or chronic gastrointestinal diseases.
• History or presence of interstitial lung disease, emphysema, chronic obstructive pulmonary disease, pulmonary interstitial fibrosis, drug-induced interstitial lung disease, or radiation pneumonitis; or uncontrolled respiratory symptoms prior to the first dose of study drug.
• Clinically significant cardiovascular disease, including but not limited to:

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead
• Beijing Baiyang Zhihe Medical Technology Transfer Services Co., Ltd.: collaborator
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yehui Shi

CONTACT

18622221183; 18526812877@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Department

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 4, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share