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.
Phase I: To determine the optimal timing for combining LITT and pembrolizumab in
patients with rGBM:
• To determine the feasibility, safety, tolerability and side effect profiles for
combining LITT and pembrolizumab at various time points pre-LITT vs. post-LITT (Phase
2. Phase II: To estimate the response to pembrolizumab combined with LITT in patients with
• To estimate the response rate after treatment with LITT combined with pembrolizumab in
patients with rGBM (Phase II).
3. To collect and record the side effect profiles for combining LITT and pembrolizumab
(Phase I and Phase II).
To determine the effect of pembrolizumab on systemic immune microenvironment in patients
To determine the effect of pembrolizumab on the intra-tumoral immunosuppressive
microenvironment within rGBM.
Secondary for Phase II, to estimate progression free survival (PFS) and overall survival
(OS) after treatment with LITT combined with pembrolizumab in patients with rGBM (Phase
Measure radiological response using both conventional RANO criterion, a modified RANO
(RANOi) designed specifically for immunotherapy response assessment, as well as MRI
fingerprinting (MRF), recently demonstrated by the PI and collaborators to accurately
and precisely distinguish recurrent GBM from radiation injury.
Correlate clinical and radiological response to known biomarkers of GBM such as
Isocitrate Dehydrogenase 1 (IDH-1) mutations, Isocitrate Dehydrogenase 2 (IDH-2)
mutations, Methyl-Guanine Methyl Transferase (MGMT) promoter methylation, Phosphatase
and tensin homologue (PTEN) loss and KI-67.
The Phase I component will involve up to two of a possible 3 cohorts of 3-4 patients each for
a total of 6-8 evaluable patients. Each patient will undergo a stereotactic biopsy. If GBM or
Gliosarcoma is confirmed by frozen section, patients will undergo LITT then treatment with
200 mg pembrolizumab IV. Cohort I will receive pembrolizumab on post operative day 14 and
every 3 weeks thereafter. In the event that one patient suffers non-hematologic toxicity of
grade 3 or more, or if hematologic toxicity is grade 4 or higher, the investigators will
delay the 2nd dose of pembrolizumab by 3 weeks and a 4th patient will be accrued. If there
are two patients in the initial cohort with non-hematologic toxicities grade 3, or if
hematological toxicity in two patients is grade 4 or higher, the second cohort will delay
initiation of pembrolizumab until post operative day 35 after LITT. Conversely, if there are
no non-hematologic adverse events (AEs) of grade 3 or higher, the investigators will proceed
to cohort IB using the same dose of pembrolizumab given 7 days prior to surgery, then every 3
weeks. Similarly, feasibility and safety will be addressed as above in deciding whether or
not to proceed to the next cohort.
The Phase II component of the study will consist of additional patients receiving
pembrolizumab at the earliest tolerated time post LITT:
14 days post-op
-7 days pre-op;
35 days post-opto achieve a total of 23 evaluable patients at the earliest tolerated
Pembrolizumab at 7 days prior,
Pembrolizumab at 14 days post,
Pembrolizumab at 35 days post,
Laser Interstitial Thermotherapy
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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