LITT + Pembrolizumab for Glioblastoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Breakthrough Therapy
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.
12345Is 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.
13467How 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.
12345Eligibility 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.
+16 more
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
+16 more
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
Participant Groups
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).
3Treatment groups
Experimental Treatment
Group I: Pembrolizumab injections 7 days before surgeryExperimental Treatment2 Interventions
Patients will have intravenous pembrolizumab 7 days before surgery with Laser Interstitial Thermotherapy
Group II: Pembrolizumab injections 35 days after surgeryExperimental Treatment2 Interventions
Patients will have intravenous pembrolizumab 35 days after surgery with Laser Interstitial Thermotherapy
Group III: Pembrolizumab injections 14 days after surgeryExperimental Treatment2 Interventions
Patients will have intravenous pembrolizumab 14 days after surgery with Laser Interstitial Thermotherapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University Hospitals Cleveland Medical Center, Case Comprehensive Cancer CenterCleveland, OH
Loading ...
Who Is Running the Clinical Trial?
Case Comprehensive Cancer CenterLead Sponsor
References
Prolonged response of recurrent IDH-wild-type glioblastoma to laser interstitial thermal therapy with pembrolizumab. [2023]Despite the improved understanding of the molecular and genetic heterogeneity of glioblastoma, there is still an unmet need for better therapeutics, as treatment approaches have remained unchanged in recent years. Research into the role of the immune microenvironment has generated enthusiasm for testing immunotherapy (specifically, immune checkpoint inhibitors). However, to date, trials of immunotherapy in glioblastoma have not demonstrated a survival advantage. Combination approaches aimed at optimally inducing response to immune checkpoint inhibitors with radiotherapy are currently being investigated. Herein, the authors describe their experience of the potential benefit and clinical outcomes of using combination pembrolizumab (an immune checkpoint inhibitor) and laser interstitial thermal therapy in a case series of patients with recurrent IDH-wild-type glioblastoma.
Window-of-opportunity clinical trial of pembrolizumab in patients with recurrent glioblastoma reveals predominance of immune-suppressive macrophages. [2021]We sought to ascertain the immune effector function of pembrolizumab within the glioblastoma (GBM) microenvironment during the therapeutic window.
Treatment with pembrolizumab in programmed death ligand 1-positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE-028 trial. [2021]Current treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of the anti-programmed death 1 (anti-PD-1) immunotherapy, pembrolizumab, in programmed death ligand 1 (PD-L1)-positive, recurrent glioblastoma.
Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit.
Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. [2022]VEGF is upregulated in glioblastoma and may contribute to immunosuppression. We performed a phase II study of pembrolizumab alone or with bevacizumab in recurrent glioblastoma.
FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]On December 18, 2015, the FDA granted regular approval to pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) for treatment of patients with unresectable or metastatic melanoma based on results of two randomized, open-label, active-controlled clinical trials. In trial PN006, 834 patients with ipilimumab-naïve metastatic melanoma were randomized (1:1:1) to pembrolizumab 10 mg/kg i.v. every 2 or 3 weeks until disease progression or ipilimumab 3 mg/kg every 3 weeks for up to four doses. In trial PN002, 540 patients with ipilimumab-refractory metastatic melanoma were randomized (1:1:1) to pembrolizumab 2 or 10 mg/kg i.v. every 3 weeks or to investigator's choice of chemotherapy. In trial PN006, patients randomized to pembrolizumab demonstrated a statistically significant improvement in overall survival compared with ipilimumab [every-2-week arm: hazard ratio (HR) = 0.63; 95% confidence interval (CI), 0.47-0.83; P < 0.001; every-3-week arm: HR = 0.69; 95% CI, 0.52-0.90; P = 0.004]. In both trials, patients receiving pembrolizumab demonstrated statistically significant improvements in progression-free survival. The most common (≥2%) immune-mediated adverse reactions in a pooled safety analysis were hypothyroidism, pneumonitis, and hyperthyroidism. Key considerations for approval were determination of pembrolizumab dose and interpretation of tumor response-based endpoints using RECIST or immune-related RECIST. Clin Cancer Res; 23(19); 5661-5. ©2017 AACR.
FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]On September 4, 2014, the FDA approved pembrolizumab (KEYTRUDA; Merck Sharp & Dohme Corp.) with a recommended dose of 2 mg/kg every 3 weeks by intravenous infusion for the treatment of patients with unresectable or metastatic melanoma who have progressed following treatment with ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. Approval was based on demonstration of objective tumor responses with prolonged response durations in 89 patients enrolled in a randomized, multicenter, open-label, dose-finding, and activity-estimating phase 1 trial. The overall response rate (ORR) by blinded independent central review per RECIST v1.1 was 24% (95% confidence interval, 15-34); with 6 months of follow-up, 86% of responses were ongoing. The most common (≥20%) adverse reactions were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea. Immune-mediated adverse reactions included pneumonitis, colitis, hepatitis, hypophysitis, and thyroid disorders. The benefits of the observed ORR with prolonged duration of responses outweighed the risks of immune-mediated adverse reactions in this life-threatening disease and represented an improvement over available therapy. Important regulatory issues in this application were role of durability of response in the evaluation of ORR for accelerated approval, reliance on data from a first-in-human trial, and strategies for dose selection. Clin Cancer Res; 23(19); 5666-70. ©2017 AACR.