LITT + Pembrolizumab for Glioblastoma

Overseen By Tiffany Hodges, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Case Comprehensive Cancer Center

Must not be taking: Immunotherapy, Anti-PD-1, Anti-PD-L1

Disqualifiers: Autoimmune disease, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects and safety of combining Laser Interstitial Thermotherapy (LITT), a minimally invasive laser technique for heating brain tumors, with Pembrolizumab, a drug that helps the immune system fight cancer. The focus is on treating glioblastoma, an aggressive brain cancer. Participants will receive Pembrolizumab injections at different times relative to their LITT surgery. This trial may suit those diagnosed with glioblastoma or gliosarcoma confined to a specific brain area and who have completed chemoradiation therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this innovative combination therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that patients should not be using steroids for at least 7 days prior to trial treatment, unless it's a physiologic replacement dose. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Laser Interstitial Thermotherapy (LITT) often provides a safe way to treat brain tumors. Studies indicate that LITT can effectively shrink tumors in many cases. In one study, LITT successfully treated tumor areas in about 93% of patients. However, tumors regrew in about 80% of cases, indicating it might not work for everyone.

The FDA has approved pembrolizumab for treating other types of cancer, confirming a certain level of safety. Although not yet approved for brain tumors, research on similar treatments suggests it can be safe to use. Some studies found that using pembrolizumab with other therapies can help the immune system better recognize and fight tumors.

In summary, LITT is generally considered a safe treatment for brain tumors. Pembrolizumab, already used for other cancers, appears safe when combined with other treatments, but its effectiveness for brain tumors remains under study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Laser Interstitial Thermotherapy (LITT) with Pembrolizumab for treating glioblastoma because this approach targets tumors in a novel way. Traditional treatments like surgery, radiation, and chemotherapy primarily focus on removing or directly destroying tumor cells. However, LITT uses precision lasers to heat and destroy cancer cells, minimizing damage to surrounding brain tissue. Meanwhile, Pembrolizumab, an immunotherapy drug, boosts the body's immune system to recognize and attack cancer cells. This combination not only directly targets and destroys the tumor but also empowers the immune system to fight residual cancer cells, offering a potentially more effective treatment with fewer side effects.

What evidence suggests that this trial's treatments could be effective for glioblastoma?

This trial will explore combining Laser Interstitial Thermotherapy (LITT) with pembrolizumab to treat glioblastoma. Studies have shown that LITT can shrink tumors and improve survival rates in glioblastoma patients who cannot undergo surgery. Specifically, patients treated with LITT often live longer without disease progression and have better overall survival rates. Pembrolizumab has shown promise in treating other cancers by aiding the immune system in fighting cancer cells. Some research suggests pembrolizumab can extend the time patients live without disease worsening and improve overall survival in various cancers. However, its effectiveness for glioblastoma remains under study, as past research has shown mixed results. In this trial, participants will receive pembrolizumab at different intervals relative to LITT surgery, potentially offering a new approach to tackling glioblastoma from multiple angles. ^{1 5 6 7 8}

Who Is on the Research Team?

Tiffany Hodges, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with confirmed glioblastoma or gliosarcoma who've completed standard chemoradiation. They must have good organ function, a Karnofsky performance status of ≥60, and be able to consent. Women of childbearing potential must test negative for pregnancy and agree to contraception. The tumor should be treatable with LITT, unifocal & unilateral, and not exceed 6 cm in diameter.

Inclusion Criteria

My surgeon believes over 90% of my tumor can be treated with a specific heat therapy.

My blood and organ function tests are within normal ranges.

My kidney function is normal as tested within the last week.

Exclusion Criteria

I have an autoimmune disease treated with medication in the last 2 years.

I have or had lung inflammation not caused by an infection.

Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants undergo LITT followed by pembrolizumab administration at various time points to determine optimal timing and safety

Up to 24 months

Multiple visits for treatment and monitoring

Phase II Treatment

Additional patients receive pembrolizumab at the earliest tolerated time post-LITT to estimate response rates

Up to 24 months

Regular visits every 3 weeks for pembrolizumab administration

Follow-up

Participants are monitored for progression-free survival and overall survival

Up to 24 months

Regular follow-up visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Laser Interstitial Thermotherapy
• Pembrolizumab

Trial Overview The study tests the effectiveness and side effects of combining Laser Interstitial Thermotherapy (LITT), a minimally invasive surgery using lasers on brain tumors, with Pembrolizumab—an immune system-boosting drug—to treat recurrent Glioblastoma Multiforme (GBM).

How Is the Trial Designed?

Group I: Pembrolizumab injections 7 days before surgery Experimental Treatment 2 Interventions

Patients will have intravenous pembrolizumab 7 days before surgery with Laser Interstitial Thermotherapy

Group II: Pembrolizumab injections 35 days after surgery Experimental Treatment 2 Interventions

Patients will have intravenous pembrolizumab 35 days after surgery with Laser Interstitial Thermotherapy

Group III: Pembrolizumab injections 14 days after surgery Experimental Treatment 2 Interventions

Patients will have intravenous pembrolizumab 14 days after surgery with Laser Interstitial Thermotherapy

Who Is Running the Clinical Trial?

Case Comprehensive Cancer Center

Lead Sponsor

Trials

472

Recruited

33,400+

Published Research Related to This Trial

In a study of 26 patients with recurrent glioblastoma, pembrolizumab showed an overall response rate of 8%, with two patients experiencing partial responses lasting up to 22.8 months, indicating some durable antitumor activity.

While 73% of patients experienced treatment-related adverse events, most were manageable, suggesting that pembrolizumab has a safety profile that allows for further exploration in combination therapies to enhance efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. Reardon, DA., Kim, TM., Frenel, JS., et al.[2021]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

In a phase II study involving 80 patients with recurrent glioblastoma, pembrolizumab combined with bevacizumab showed a 6-month progression-free survival (PFS-6) of 26% and a median overall survival (OS) of 8.8 months, indicating limited efficacy despite being well tolerated.

Pembrolizumab alone had a much lower PFS-6 of 6.7% and no objective responses, suggesting that while the combination therapy had some durable responses, neither treatment was effective enough for significant clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Nayak, L., Molinaro, AM., Peters, K., et al.[2022]

Current treatments for glioblastoma have not significantly changed despite advances in understanding its molecular and genetic diversity, highlighting the need for better therapeutic options.

In a case series, combining pembrolizumab, an immune checkpoint inhibitor, with laser interstitial thermal therapy showed potential benefits for patients with recurrent IDH-wild-type glioblastoma, suggesting a promising direction for future treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. Hwang, H., Huang, J., Khaddour, K., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39528836/

Evaluating efficacy and safety of laser interstitial thermal ... LITT shows promise for treating both newly diagnosed and recurrent GB cases in non-surgical candidates, linked to improved OS, PFS, reduced tumor volume, and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9122789/

Efficacy of laser interstitial thermal therapy (LITT) for newly ... Numerous retrospective studies have reported the utility of LITT for the management of newly diagnosed and recurrent glioblastoma. These studies have ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05318612

NCT05318612 | Effectiveness of MR-guided LITT Therapy ... The aim of this study is to investigate the (cost-)effectiveness of LITT (Laser Interstitial Thermal Therapy) in primary irresectable glioblastoma.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0303846720302857

Survival outcomes in patients with recurrent glioblastoma ... The median progression-free survival and the median overall survival after laser interstitial thermal therapy resulted 5.6 months and 10.2 months, respectively.

5. thejns.org thejns.org/focus/view/journals/neurosurg-focus/57/5/article-pE4.xml

An analysis of functional outcomes following laser interstitial ... The majority of patients undergoing LITT for recurrent HGG had a favorable functional outcome at the initial follow-up visit. The treated tumor volume was ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11171930/

Safety and Efficacy of Laser Interstitial Thermal Therapy as ... The pooled data suggest LITT may be a safe primary management option with tumor ablation rates of 94.8% and 84.6% in IDH-wildtype glioblastoma ...

7. journals.lww.com journals.lww.com/neurosurgery/fulltext/2019/04000/glioblastoma_treated_with_magnetic_resonance.3.aspx

Glioblastoma Treated With Magnetic Resonance Imaging ... Overall, we were able to achieve an average of 93% of tumor volume treatment within the yellow TDT line and 88% treatment with the blue TDT line, concordant ...

8. thejns.org thejns.org/focus/view/journals/neurosurg-focus/59/2/article-pE10.xml

Laser interstitial thermal therapy for high-grade glioma Tumor progression after LITT was observed in approximately 80.0% of patients (95% CI 61.9%–93.8%), and the overall mortality rate was 67.7% (95% CI 47.5%–85.2%) ...