Laser Interstitial Thermal Therapy (LITT) and Lomustine (CCNU) for Recurrent Glioblastoma

Inclusion Criteria:

1. Histologically confirmed World Health Organization (WHO) 2021 defined glioblastoma.A pathology report constitutes adequate documentation of histology for studyinclusion.

2. Radiographic demonstration of disease progression following prior therapy.

3. Patients having undergone recent resection of recurrent or progressive tumor will beeligible as long as the patient has recovered from surgery. Evaluable or measurabledisease following resection of recurrent tumor is not mandated for eligibility intothe study.

4. Prior standard radiation for glioblastoma (short course 40 Gy, standard 60 Gy, andproton therapy are allowed).

5. Patients must have recovered from the effects of prior therapy.

6. The following listed agents/interventions must have been discontinued for theirrespective time period prior to enrollment:

7. Four weeks from cytotoxic agents (3 weeks from procarbazine, 3 weeks fromvincristine, and 4 weeks from temozolomide);

8. Four weeks or 5 drug half-lives (whichever is shorter) from any investigationalagent; two weeks or 5 drug half-lives (whichever is shorter) from non-cytotoxicagents (e.g. Accutane, thalidomide);

9. Twelve weeks from radiotherapy to minimize the potential for MRI changesrelated to radiation necrosis that might be misdiagnosed as progressivedisease, or 4 weeks if a new lesion, relative to the pre-radiation MRI,develops that is outside the primary radiation field;

10. Patients must have the following laboratory parameters ≤ 14 days prior toregistration: a. adequate bone marrow function defined by: i. white blood cells (WBC) ≥ 3 × 109/L , ii. absolute neutrophil count (ANC) ≥ 1.5 × 109/L , iii. platelet count of ≥ 100 × 109/L , and iv. hemoglobin ≥ 9 gm/dL b. adequate liver function defined by i.alanine transaminase (ALT, SGPT) and aspartate transaminase (AST/SGOT) < 3×institutional upper limit of normal (ULN), ii. alkaline phosphatase < 2× ULN, andiii. bilirubin < 1.5 mg/dL c. adequate renal function defined by calculatedcreatinine clearance ≥ 60 mL/min (see Appendix)

11. Karnofsky performance status (KPS) ≥ 50 (see Appendix).

12. Individuals of childbearing potential or those with partners of childbearingpotential must agree to use adequate methods of contraception for the duration ofstudy participation (including dosing interruptions) and for up to 3.5 months afterthe last study treatment; or be surgically sterilized.

13. Patients on the following medications are allowed:

14. Anticoagulants: Patients on stable dose anticoagulants (e.g. warfarin in-rangeinternational normalized ratio [INR], low molecular-weight heparin)

15. Patients are allowed to take aspirin, clopidogrel, ticlopidine, Aggrenox,ibuprofen and other NSAIDS.

16. Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapyfor glioblastoma while enrolled in the study.

17. Able to swallow oral medication.

18. Patients ≥18 years of age at time of consent.

19. Ability to understand and willingness to sign an informed consent form (ICF).

20. Ability and stated willingness to adhere to the study visit schedule and protocolprocedures/requirements, including periodic blood sampling and study relatedassessments

Exclusion Criteria:

1. Patients who are not surgical candidates for stereotactic biopsy or laser ablation.

2. Prior treatment with nitrosourea agents (e.g. lomustine [CCNU], carmustine [BCNU],nimustine [ACNU]).

3. Prior treatment with polifeprosan 20 with carmustine wafer.

4. Prior treatment with bevacizumab.

5. Patients who have received any investigational agents ≤ 4 weeks or 5 drug half-lives (whichever is shorter) prior to commencing study treatment.

6. Evidence of recent hemorrhage on baseline MRI of the brain with the followingexceptions: (1) presence of hemosiderin, (2) resolving hemorrhagic changes relatedto surgery, or (3) presence of punctate hemorrhage in the tumor.

7. History of intracerebral abscess within 6 months prior to Day 1.

8. Major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 daysprior to Day 1, or anticipation of the need for a major surgical procedure duringthe course of the study.

9. Serious non-healing wound, ulcer, or bone fracture.

10. Pregnancy (positive pregnancy test) or lactation.

11. Known hypersensitivity to any component of lomustine (CCNU).

12. Uncontrolled intercurrent illness or unstable systemic disease, including, but notlimited to, ongoing or active infection, uncontrolled hypertension, or seriouscardiac arrhythmia requiring medication that would interfere with participant safetyor limit compliance with the study requirements.

13. Unable to undergo an MRI with contrast.

14. Known allergy to nitrosoureas (e.g., lomustine, carmustine, nimustine).

15. Any condition that in the opinion of the investigator would interfere with theparticipant's safety or compliance while on trial