A Prospective, Randomized, Standard of Care Controlled, Parallel, Open-Label, Multicenter Pivotal Study to Evaluate the Efficacy and Safety of Avastin® in Combination With NaviFUS System Compared With Avastin® Alone for the Treatment of Recurrent Glioblastoma Multiforme (rGBM)

Plain English Summary

A Prospective Pivotal Study to Evaluate the Efficacy and Safety of Avastin® Bevacizumab (BEV) With or Without Microbubble-mediated Focused Ultrasound (FUS-MB) Using NaviFUS System in Recurrent Glioblastoma Multiforme Patients is a Phase 3 clinical trial sponsored by NaviFUS Corporation studying Glioblastoma Multiforme, Glioblastoma, Glioblastoma Multiforme, Adult, Glioma, Brain Tumor, Brain Tumor, Recurrent, Neoplasms, Neoplasms, Nerve Tissue. Tests the effectiveness and safety of Avastin® with or without microbubble-mediated focused ultrasound (FUS-MB) in treating recurrent glioblastoma. For patients over 18 with recurrent glioblastoma who have had previous treatments. Participation involves regular medical check-ups and treatments, including Avastin® infusions and possible FUS-MB. Alternative treatments include standard care with Avastin® alone. The trial aims to enroll 32 participants.

Official Summary

This will be a prospective, randomized, standard of care (SoC) controlled, parallel, open-label, multicenter pivotal study to investigate the efficacy and safety of Bevacizumab (BEV) in combination with or without microbubble (MB)-mediated FUS in patients with recurrent GBM. BEV represents the physician's best choice for the standard of care in rGBM after previous treatment with surgery (if appropriate), standard radiotherapy with temozolomide chemotherapy, and with adjuvant temozolomide.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 18, with recurrent glioblastoma, and have had previous treatments. Not eligible if have multifocal tumors, previous anti-angiogenic therapy, or significant cardiovascular issues. Age: 18 years and older. Health: Good overall health, no significant heart or stroke history. This trial is studying Glioblastoma Multiforme, Glioblastoma, Glioblastoma Multiforme, Adult, Glioma, Brain Tumor, Brain Tumor, Recurrent, Neoplasms, Neoplasms, Nerve Tissue, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures survival and response rates, which can mean longer life and better treatment options for patients. The specific primary outcome measures are: 6-month progression-free survival (PFS-6) of Bevacizumab (BEV) with or without microbubble-mediated focused ultrasound (FUS-MB) using NaviFUS System (Up to 6 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial fills a gap by testing a new combination therapy for recurrent glioblastoma, potentially offering better outcomes. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Glioblastoma Multiforme, Glioblastoma, Glioblastoma Multiforme, Adult, Glioma, Brain Tumor, Brain Tumor, Recurrent, Neoplasms, Neoplasms, Nerve Tissue, where improved treatment options are needed.

Investor Insight

Market size is significant, with a competitive landscape and a high probability of approval given the unmet need in glioblastoma treatment. Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor about your eligibility and the potential benefits and risks of the study. Participation involves regular medical check-ups, Avastin® infusions, and possible FUS-MB treatments. This trial is currently recruiting participants. The trial is being conducted at 2 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: SINGLE
• Enrollment: 32 participants

Interventions

• DRUG: Bevacizumab — An anti-angiogenic agent to block tumor growth
• DRUG: Microbubble — Open the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble
• DEVICE: Low-Intensity Focused Ultrasound — Open the Blood-Brain Barrier (BBB) using focused ultrasound and microbubble

Primary Outcomes

• 6-month progression-free survival (PFS-6) of Bevacizumab (BEV) with or without microbubble-mediated focused ultrasound (FUS-MB) using NaviFUS System (Up to 6 months)

Secondary Outcomes

• 12-month progression-free survival (PFS-12) (Up to 12 months)
• Progression-free survival time (PFS) (Up to 62 weeks)
• One- and Two-year survival rates (Up to 12 and 24 months)
• Overall survival (OS) (Up to 36 months)
• Objective response rate (ORR) (Up to 62 weeks)

Full Eligibility Criteria

Inclusion Criteria:

1. Male or female patients ≥ 18 years of age at the time of study enrollment.
2. Body mass index (BMI) ≥ 17 kg/m2.
3. Patients diagnosed with glioblastoma must have unequivocal evidence of recurrence, as determined by contrast-enhanced magnetic resonance imaging (CE-MRI), following prior radiotherapy and temozolomide chemotherapy.
4. Patients may have undergone surgery for recurrence. The patients should have completed surgery and adequately recovered prior to the time of study enrollment.
5. Patients must have radiographic evidence of either at least an 80% resection of enhancing tumor following recurrence or a maximal measurable residual tumor ≤ 20 cm3.
6. If patients are receiving corticosteroids, they must have been on a stable or decreasing dose of corticosteroids for at least 1 week prior to the planned first treatment.
7. At the time of study enrollment, the minimum interval since the last event:

   * 4 weeks out from invasive procedures (e.g., open biopsy, surgical resection, significant traumatic injury, or any other major surgery involving entry into a body cavity) and the patient must have recovered from the effects of surgery
   * 1 week out from minor surgical procedures or core biopsies
8. Patients must have recovered from the toxic effects of prior therapy at the time of study enrollment as follows:

   * 4 weeks out from any investigational drug or device
   * 4 weeks out from chemotherapy
   * 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen (e.g., Carmustine (BCNU))
   * 12 weeks out from completion of radiotherapy
9. Patients should have a life expectancy ≥ 12 weeks.
10. Patients must have Karnofsky Performance Status (KPS) ≥ 70.
11. Adequate hematopoietic, renal, hepatic, and coagulation function, defined as:

    * Hemoglobin ≥ 10 g/dL
    * Platelets ≥ 100,000/mm3
    * Neutrophils ≥ 1,500/mm3
    * Serum creatinine ≤ 1.5 × upper limit of normal (ULN)
    * Urine protein creatinine ratio (UPCR) \< 1 or urine dipstick for proteinuria ≤ 2+
    * Alanine aminotransferase (ALT) \< 3 × ULN
    * Aspartate aminotransferase (AST) \< 3 × ULN
    * Total bilirubin (TBL) \< 2 × ULN
    * Prothrombin time ≤ 1.5 x ULN
    * International Normalized Ratio (INR) \< 1.5 These tests must be conducted within 2 weeks prior to the planned first treatment.
12. The central of FUS exposure region is located with a minimum distance of at least 30 mm beneath the skull bone.
13. Females of childbearing potential must have a negative pregnancy test documented within 2 weeks prior to first treatment. Females of childbearing potential and male patients with partners of childbearing potential must agree to adhere to an acceptable method of contraception (as outlined below) from prior to the first study treatment until at least 6 months after the completion of last treatment. Standard acceptable methods of contraception include the use of highly effective methods such as hormonal contraception, diaphragm, cervical cap, vaginal sponge, condom, spermicide, vasectomy, intrauterine device, or abstinence from sexual activity.
14. Patients are able and willing to have peripheral intravenous (IV) line placement of Bevacizumab and are able to have hair shaved (either whole head or in the region where the coupling membrane will touch) prior to FUS treatment if assigned to treatment group.
15. Patients or their legal representatives are able to provide written informed consent for participation in the trial and patients are willing to comply the procedures (i.e., study-related assessments), instructions, and restrictions outlined in this study in the duration of the study. Informed consent should also be given for biological materials and diagnostic imaging to be stored and used for future research on brain tumors.

Exclusion Criteria:

1. Patients who have radiographic evidence of multifocal enhancing tumors.
2. Patients who have undergone previous treatment with anti-angiogenic therapy, including Bevacizumab, or other VEGF inhibitors or VEGF-receptor signaling inhibitors.
3. Patients who have previously received Carmustine wafers implantation during re-operation.
4. Patients who have previously received or are currently undergoing tumor treating fields (TTF) treatment.
5. Uncontrolled or significant cardiovascular disease, including any of the following:

   * New York Heart Association (NYHA) Grade II or above congestive heart failure (CHF) within 12 months prior to study enrollment
   * Unstable angina pectoris
   * Medical history of myocardial infarction within 6 months prior to study enrollment
   * Cardiac shunt
6. Stroke (except for transient ischemic attack; TIA) within 6 months prior to study enrollment.
7. Patients with implanted electronic device, for example, implanted cardioverter-defibrillator (ICD), cardiac pacemaker, permanent medication pumps, cochlear implants, responsive neurostimulator (RNS), deep brain stimulation (DBS), or other electronic devices imp

Trial Locations

• National Taiwan University Hospital, Taipei, Taiwan
• Linkou Chang Gung Memorial Hospital, Taoyuan District, Taiwan

Frequently Asked Questions

Related Conditions

• Recurrent glioblastoma, glioblastoma, glioblastoma multiforme, glioma, brain tumor, brain tumor, recurrent brain tumor, neoplasms, nerve tissue neoplasms

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