30 Participants Needed

Focused Ultrasound + Immunotherapy for Brain Cancer

(LIMITLESS Trial)

Recruiting at 3 trial locations
NA
Overseen ByNadir Alikacem
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: InSightec
Must be taking: Immune checkpoint inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise
Approved in 3 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the treatment of NSCLC brain metastases in patients who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on Bevacizumab (Avastin) or certain immunosuppressive therapies, you may not be eligible to participate.

What data supports the effectiveness of the treatment Focused Ultrasound + Immunotherapy for Brain Cancer?

Pembrolizumab, a part of the treatment, has shown effectiveness in treating various cancers, including melanoma and lung cancer, by helping the immune system attack cancer cells. In studies, it has demonstrated significant tumor response rates and prolonged response durations, suggesting potential benefits in treating brain cancer as well.12345

Is the combination of focused ultrasound and pembrolizumab (Keytruda) generally safe for humans?

Pembrolizumab (Keytruda) has been approved for use in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, and nausea, and more serious immune-related issues like pneumonitis (lung inflammation) and thyroid problems. While focused ultrasound safety data isn't provided here, pembrolizumab's safety profile is well-documented in cancer treatments.14678

What makes the treatment of focused ultrasound combined with pembrolizumab unique for brain cancer?

This treatment is unique because it combines focused ultrasound, a non-invasive technique that uses sound waves to target tumors, with pembrolizumab, an immunotherapy drug that helps the immune system attack cancer cells by blocking a protein called PD-1. This combination aims to enhance the effectiveness of the immune response against brain cancer, which is different from traditional treatments that may not involve the immune system.1491011

Research Team

MA

Manmeet Ahluwalia, MD, MBA

Principal Investigator

Miami Cancer Institute, Baptist Health South Florida

Eligibility Criteria

Adults with non-small cell lung cancer (NSCLC) brain metastases, not pregnant, willing to use contraception and comply with study procedures. Must have EGFR/ALK-negative tumors, measurable untreated brain metastasis accessible by MRI, good performance status (Karnofsky ≥70% or ECOG 0-2), and prescribed pembrolizumab. Excludes those with bleeding risks, certain infections like hepatitis/HIV/TB, severe medical disorders, known allergies to trial substances, contraindications to MRI/gadolinium-DTPA or pembrolizumab.

Inclusion Criteria

I am not pregnant and will use effective birth control during and 4 months after the study.
Participant is willing to comply with all study procedures for the duration of the study
I can take care of myself and perform normal activities.
See 6 more

Exclusion Criteria

I am allergic or cannot take pembrolizumab due to severe reactions.
I have not received a live vaccine in the last 28 days.
I have an autoimmune disease treated in the last 2 years or currently have pneumonitis.
See 20 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ICI Systemic Therapy with Exablate BBBO or ICI Systemic Therapy alone every 3 weeks for 6 cycles

18 weeks
6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of tumor response and adverse events

up to 6 months
Every 3 weeks

Treatment Details

Interventions

  • Exablate Model 4000 Type 2.0/2.1
  • Pembrolizumab
Trial OverviewThe trial is testing the safety and effectiveness of disrupting the blood-brain barrier using Exablate Focused Ultrasound in combination with standard pembrolizumab therapy for treating NSCLC brain metastases. The goal is to see if this approach can improve treatment outcomes.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: ICI Systemic Therapy with Exablate BBBOExperimental Treatment6 Interventions
Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.
Group II: Control Arm (ICI Systemic Therapy on-label use only)Active Control5 Interventions
subjects will undergo planned on-label ICI Systemic Therapy.

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

🇺🇸
Approved in United States as KEYTRUDA for:
  • Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
  • Melanoma
  • Non-small cell lung cancer (NSCLC)
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Hepatocellular carcinoma
  • Renal cell carcinoma
  • Cervical cancer
  • Endometrial carcinoma
🇪🇺
Approved in European Union as KEYTRUDA for:
  • Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
  • Melanoma
  • Non-small cell lung cancer (NSCLC)
  • Urothelial carcinoma
  • Colorectal cancer
  • Gastric cancer
  • Hepatocellular carcinoma
  • Renal cell carcinoma
  • Cervical cancer
  • Endometrial carcinoma
🇬🇧
Approved in United Kingdom as KEYTRUDA for:
  • Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Find a Clinic Near You

Who Is Running the Clinical Trial?

InSightec

Lead Sponsor

Trials
92
Recruited
3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Findings from Research

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.
Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions.Karim, S., Leighl, N.[2017]
In a phase II trial involving 15 patients with recurrent glioblastoma, pembrolizumab treatment did not lead to significant immune activation within the tumor microenvironment, which was characterized by a lack of T cells and a predominance of CD68+ macrophages.
Despite no treatment-related deaths and a median overall survival of 20 months, the study found that pembrolizumab alone was insufficient to induce a robust immune response in most patients, suggesting that additional strategies may be needed to enhance its efficacy in glioblastoma.
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages.de Groot, J., Penas-Prado, M., Alfaro-Munoz, K., et al.[2021]
The combination of pembrolizumab, hypofractionated stereotactic irradiation (HFSRT), and bevacizumab was found to be generally safe and well tolerated in 32 patients with recurrent high-grade gliomas, with manageable treatment-related adverse events such as proteinuria and fatigue.
In the bevacizumab-naïve group, 83% of patients showed a complete or partial response, with a median overall survival of 13.45 months, indicating promising preliminary efficacy of this treatment combination.
Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study.Sahebjam, S., Forsyth, PA., Tran, ND., et al.[2021]

References

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]
Hypofractionated stereotactic re-irradiation with pembrolizumab and bevacizumab in patients with recurrent high-grade gliomas: results from a phase I study. [2021]
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]
Pembrolizumab superior to ipilimumab in melanoma. [2017]
Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]
Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]
FDA Approves Pembrolizumab for BCG-Unresponsive NMIBC. [2021]
Pembrolizumab: first global approval. [2021]
Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. [2022]