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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the side effects and efficacy of using Laser Interstitial Thermotherapy (LITT) combined with Pembrolizumab. LITT is a minimally invasive surgical technique that uses a laser to heat brain tumors. Pembrolizumab is an investigational (experimental) drug that works by helping participants' immune system work correctly to detect and fight cancer cells. Pembrolizumab is experimental because it is not approved by the Food and Drug Administration (FDA), for this use, though it is approved to treat other cancers.

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.

What data supports the effectiveness of the treatment LITT + Pembrolizumab for Glioblastoma?

Research has shown that pembrolizumab, an immune therapy drug, has some antitumor activity in certain types of glioblastoma, and combining it with laser interstitial thermal therapy may offer potential benefits, as seen in a case series of patients with recurrent glioblastoma. ^{1 2 3 4 5}

Is the combination of LITT and pembrolizumab safe for humans?

Pembrolizumab (also known as KEYTRUDA or MK-3475) has been used in various clinical trials for different cancers, showing some common side effects like fatigue, cough, nausea, and rash. More serious immune-related side effects can include lung inflammation (pneumonitis), liver inflammation (hepatitis), and thyroid problems. While these studies provide safety data for pembrolizumab, specific safety data for its combination with Laser Interstitial Thermotherapy (LITT) in glioblastoma is limited. ^{1 3 4 6 7}

How is the treatment LITT + Pembrolizumab for glioblastoma different from other treatments?

This treatment combines laser interstitial thermal therapy (LITT), which uses heat to destroy tumor cells, with pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. This combination is unique because it aims to enhance the immune response against glioblastoma, a strategy not typically used in standard treatments for this condition. ^{1 2 3 4 5}

Research Team

Tiffany Hodges, MD

Principal Investigator

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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 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, 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]