Laser Interstitial Thermotherapy (LITT) Combined With Checkpoint Inhibitor for Recurrent GBM (RGBM)

NCT03277638 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CASE3316NCI-2017-02417
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Glioblastoma, Adult

Keywords

recurrent glioblastoma; brain cancer

Outcome Measures

Primary Outcomes (2)

• Phase I endpoint: Optimal timing of LITT with pembrolizumab

  Optimal timing of LITT with pembrolizumab

  Up to 24 months after beginning Pembrolizumab

• Phase II endpoint: Tumor Response

  Response rates for the Phase II component will be calculated and compared to historical controls using chi-square tests or Fishers exact tests.

  Up to 24 months after beginning Pembrolizumab

Secondary Outcomes (5)

• Progression free survival (PFS)

  Up to 24 months after beginning Pembrolizumab

• Overall survival (OS)

  Up to 24 months after beginning Pembrolizumab

• The proportion of patients who achieve progression free survival at 6 months (PFS6)

  Up to 6 months after diagnosis

• The proportion of patients who achieve progression free survival at 12 months (PFS12)

  Up to 12 months after diagnosis

• The proportion of patients who achieve progression free survival at 24 months (PFS24)

  Up to 24 months after diagnosis

Study Arms (3)

Pembrolizumab injections 7 days before surgery

EXPERIMENTAL

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

Drug: Pembrolizumab at 7 days prior; Procedure: Laser Interstitial Thermotherapy

Pembrolizumab injections 14 days after surgery

EXPERIMENTAL

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

Drug: Pembrolizumab at 14 days post; Procedure: Laser Interstitial Thermotherapy

Pembrolizumab injections 35 days after surgery

EXPERIMENTAL

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

Drug: Pembrolizumab at 35 days post; Procedure: Laser Interstitial Thermotherapy

Interventions

Pembrolizumab at 7 days prior DRUG

Pembrolizumab injections 7 days before surgery

Also known as: Pembrolizumab

Pembrolizumab injections 7 days before surgery

Pembrolizumab at 14 days post DRUG

Pembrolizumab injections 14 days after surgery

Also known as: Pembrolizumab

Pembrolizumab injections 14 days after surgery

Pembrolizumab at 35 days post DRUG

Pembrolizumab injections 35 days after surgery

Also known as: Pembrolizumab

Pembrolizumab injections 35 days after surgery

Laser Interstitial Thermotherapy PROCEDURE

surgical procedure to heat hard to reach tumors with a laser beam

Also known as: LITT

Pembrolizumab injections 14 days after surgery; Pembrolizumab injections 35 days after surgery; Pembrolizumab injections 7 days before surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histopathologically proven diagnosis of glioblastoma or gliosarcoma prior to registration by pathology report;
• The tumor must be confined to the supratentorial compartment
• The Formaldehyde Fixed-Paraffin Embedded tumor tissue block must be available to be sent for retrospective central pathology review after registration).
• History/physical examination within 7 days prior to registration
• Karnofsky performance status ≥ 60 within 7 days prior to registration
• Adequate Organ Function Laboratory Values
• Absolute neutrophil count (ANC) ≥1,500/mcL
• Platelets ≥100,000/mcL
• Hemoglobin ≥9.0 g/gL or ≥5.6 mmol/L, without recent transfusion
• Creatine ≤1.7 x upper limit of normal (ULN) or Measure or Calculated creatinine clearance ≥ 60.0mL/min for subject with creatinine levels \> 1.5 X institutional ULN (GFR can also be used in place of creatinine or CrCl)
• Total bilirubin ≤ 1.5 x ULN or Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 x ULN
• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN or ≤ 5 x ULN for subjects with liver metastases
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
• Adequate hematologic function based on complete blood count (CBC)/differential within 7 days prior to registration defined as follows:

You may not qualify if:

• Use of an immunotherapy such as a vaccine therapy, dendritic cell vaccine or intracavitary or convectional enhanced delivery of therapy in the past
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• Severe, active co-morbidity defined as follows:
• Unstable angina within the last 6 months prior to registration
• Transmural myocardial infarction within the last 6 months prior to registration
• Evidence of recent myocardial infarction or ischemia by the findings of S-T elevations of ≥ 2 mm using the analysis of an EKG performed within 7 days prior to registration
• New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to registration
• History of stroke, cerebral vascular accident (CVA) or transient ischemic attack within 6 months prior to registration
• Serious and inadequately controlled cardiac arrhythmia
• Significant vascular disease (e.g., aortic aneurysm, history of aortic dissection) or clinically significant peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Serious or non-healing wound, ulcer, or bone fracture or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration, with the exception of the craniotomy for tumor resection.
• Known history of Tuberculosis
• Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Lead; pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Metals

Study Officials

• Tiffany Hodges, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Because this is an open-label, safety and tolerability study in which all enrolled subjects will receive Pembrolizumab in Combination with LITT, this study is unblinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Three parallel groups given Pembrolizumab injections at different timepoints

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 11, 2017
• Study Start: November 29, 2017
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 9, 2026

Record last verified: 2026-04

Locations

US (1)