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LITT and Pembrolizumab in Recurrent Brain Metastasis (TORCH)

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ClinicalTrials.gov Identifier: NCT04187872
Recruitment Status : Recruiting
First Posted : December 5, 2019
Last Update Posted : August 23, 2022
Monteris Medical
Information provided by (Responsible Party):
University of Florida

Brief Summary:
This is an open-label, historically controlled pilot study investigating the immune effect of Laser Interstitial ThermotHerapy (LITT)+ pembrolizumab in adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis after prior stereotactic radiosurgery (SRS).

Condition or disease Intervention/treatment Phase
Melanoma Non-small Cell Lung Carcinoma (NSCLC) Renal Cell Carcinoma (RCC) Small-cell Lung Cancer Head and Neck Squamous Cell Cancer Classical Hodgkin Lymphoma Primary Mediastinal Large B-Cell Lymphoma Urothelial Carcinoma Microsatellite Instability-High Cancer Gastric Cancer Esophageal Cancer Cervical Cancer Hepatocellular Carcinoma Merkel Cell Carcinoma Brain Metastases, Adult Combination Product: LITT + Pembrolizumab Phase 1

Detailed Description:
Adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis that have failed stereotactic radiosurgery treatment will be screened. They will sign consent and complete screening procedures. Each patient will be scheduled to undergo biopsy and LITT treatment. Within two weeks of surgery, patients will begin receiving pembrolizumab every three weeks. Pembrolizumab infusions will continue until brain met recurrence per RANO for Brain Mets or up to two years, whichever comes first. Blood samples will be collected for immune monitoring. Tumor tissue will be collected for immune and genomic studies. Approximately 21 patients will be enrolled to accrue 15 evaluable subjects. Patients will be followed for survival data for one year or until death, whichever comes first.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Recurrent Brain Metastasis Immune Effects and RespOnse to Laser Interstitial ThermotHerapy (LITT) and Pembrolizumab in Combination (TORCH)
Actual Study Start Date : January 10, 2020
Estimated Primary Completion Date : January 2024
Estimated Study Completion Date : October 2025

Arm Intervention/treatment
Experimental: Patients with Recurrent Brain Metastes
Adult patients with a primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor who have recurrent brain metastasis that have failed SRS treatment will receive LITT per standard of care in combination with Pembrolizumab 200mg IV every 3 weeks (+/-3 days) up to 2 years.
Combination Product: LITT + Pembrolizumab
Each patient will undergo brain biopsy and laser interstitial thermotherapy (LITT). As soon as possible, no later than two weeks after LITT, pembrolizumab will be administered via infusion and continue q3wks for up to two years.
Other Names:
  • NeuroBlate System
  • Keytruda

Primary Outcome Measures :
  1. Immune Effect of LITT plus pembrolizumab [ Time Frame: From first dose pembro through 30 days after administration of pembro ]
    Immune profile of peripheral blood mononuclear cells (PBMCs) as measured by RNA sequencing; analysis will be performed through serial blood draws and will compare each analysis to the patient's baseline prior to treatment.

Secondary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]) of LITT plus pembrolizumab [ Time Frame: From first dose pembro to 30 days post final pembro dose ]
    Adverse events will be collected for each patient from the first dose of pembrolizumab until end of the study treatment.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  1. Histologic confirmation of primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor
  2. At least one metastatic lesion has had prior SRS. Each patient's scan must be reviewed by a neurosurgeon or radiation oncologist prior to enrollment.
  3. KPS ≥ 70.
  4. 18 years or older.
  5. Adequate bone marrow and organ function as defined below:

    1. ANC ≥ 1,500/mcL
    2. Platelets ≥ 100,000/mcL
    3. Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L (transfusion is allowed)
    4. Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine > 1.5 x IULN
    5. Serum total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total bilirubin

    i) 1.5 x IULN f) AST (SGOT) and ALT (SGPT) ≤ 3 x IULN

  6. Candidate for pembrolizumab treatment.
  7. Candidate for LITT treatment:

    1. Metastatic lesions individually measuring 3.5 cm or less
    2. Only lesions that are growing or new will be treated with LITT
    3. Five (5) or less target metastatic lesions that are new or growing
    4. Lesions accessible with a laser probe as determined by the neurosurgeon performing the procedure
    5. Patient able to undergo MRI scans (no incompatible MRI hardware, etc.)
  8. A diagnostic contrast-enhanced MRI of the brain must be performed preoperatively, within 30 days prior to study enrollment.
  9. Participants of childbearing age must use effective contraception:

    a) Women of childbearing potential (WOCBP) must be using a highly effective method of contraception to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug to minimize the risk of pregnancy. Prior to study enrollment, women of childbearing potential must be advised of the importance of avoiding pregnancy during trial participation and the potential risk factors for an unintentional pregnancy. Refer to Section 9.3 for guidance on highly effective contraceptive methods.

    i) WOCBP include any woman who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or oophorectomy) or who is not post-menopausal. Post-menopause is defined as:

(1) Amenorrhea that has lasted for ≥ 12 consecutive months without another cause, or (2) For women with irregular menstrual periods who are taking hormone replacement therapy (HRT), a documented serum follicle-stimulating hormone (FSH) level of greater than 35 mIU/mL.

b) Males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.

10. Ability of the patient to understand and willingness to sign an IRB approved written informed consent document.

11. Steroid dose equivalent to dexamethasone dose of ≤ 6mg daily at the time of enrollment.


  1. Actively participating in another clinical trial on active study treatment; follow-up or observational status is acceptable if more than 2 weeks since last study treatment.
  2. History of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (with the exception of daily dexamethasone ≤ 6 mg).
  3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection that will no resolve prior to delivery of treatment (LITT), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements.
  4. History of active autoimmune disease requiring systemic treatment within the past 2 years (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  5. Pneumonitis within the past 3 years (Note that patients with a history of pneumonitis in the past 3 years that was not aggravated by immunotherapy including immune checkpoint inhibitors or that has clinically resolved or improved and has not recurred or progressed clinically with subsequent immunotherapy including immune checkpoint inhibitors are eligible to participate in the study).
  6. Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy test at screening.
  7. Females or males of childbearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 24 weeks after the last dose of study drug.
  8. Known active hepatitis B (e.g., HBsAg reactive) or hepatitis C (e.g., HCV RNA [qualitative] is detected) infection.
  9. Known history of active TB (bacillus tuberculosis).
  10. Known history of HIV (HIV 1/2 antibodies).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04187872

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Contact: Victoria Hope 352-273-9000 victoria.hope@neurosurgery.ufl.edu

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United States, Florida
McKnight Brain Institute of the University of Florida Recruiting
Gainesville, Florida, United States, 32611
Contact: Victoria Hope    352-273-9000    victoria.hope@neurosurgery.ufl.edu   
Principal Investigator: Maryam Rahman, MD         
Sub-Investigator: David Tran, MD         
University of Florida Health Recruiting
Jacksonville, Florida, United States, 32209
Contact: Jose Alonso    904-244-9632    jose.alonso@jax.ufl.edu   
Sub-Investigator: Abhinav Rohatgi, MD         
Sub-Investigator: Adam Holtzman, MD         
Sub-Investigator: Daryoush Tavanaiepour, MD         
Sponsors and Collaborators
University of Florida
Monteris Medical
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Principal Investigator: Maryam Rahman, MD University of Florida
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Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT04187872    
Other Study ID Numbers: IRB201902411
OCR26353 ( Other Identifier: UF OnCore )
First Posted: December 5, 2019    Key Record Dates
Last Update Posted: August 23, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Florida:
Recurrent brain metastases
Additional relevant MeSH terms:
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Carcinoma, Merkel Cell
Neoplasm Metastasis
Small Cell Lung Carcinoma
Brain Neoplasms
Carcinoma, Non-Small-Cell Lung
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Microsatellite Instability
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Glandular and Epithelial
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms