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LITT and Pembrolizumab in Recurrent Brain Metastasis (TORCH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04187872
Recruitment Status : Recruiting
First Posted : December 5, 2019
Last Update Posted : February 7, 2020
Sponsor:
Collaborator:
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 patients with melanoma, non-small cell lung carcinoma (NSCLC) or renal cell carcinoma (RCC) brain metastases that recur after prior stereotactic radiosurgery (SRS).

Condition or disease Intervention/treatment Phase
Melanoma Non-small Cell Lung Carcinoma (NSCLC) Renal Cell Carcinoma (RCC) Brain Metastases 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 : 15 participants
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 2022
Estimated Study Completion Date : October 2023


Arm Intervention/treatment
Experimental: Patients with Recurrent Brain Metastes
Adult patients with primary melanoma, non-small cell lung carcinoma, or renal cell carcinoma who have recurrent brain metastes 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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
Criteria

INCLUSION CRITERIA

  1. Histologic confirmation of primary cancer approved by the FDA for treatment with an immune-checkpoint inhibitor, generally:

    1. Melanoma
    2. Non-Small Cell Lung Cancer
    3. Small Cell Lung Cancer
    4. Head and Neck Squamous Cell Cancer
    5. Classical Hodgkin Lymphoma
    6. Primary Mediastinal Large B-Cell Lymphoma
    7. Urothelial Carcinoma
    8. Microsatellite Instability-High Cancer
    9. Gastric Cancer
    10. Esophageal Cancer
    11. Cervical Cancer
    12. Hepatocellular Carcinoma
    13. Merkel Cell Carcinoma
    14. Renal Cell Carcinoma
  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.

EXCLUSION CRITERIA

  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, 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. History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  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


Contacts
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Contact: Annie Allen 352-294-8836 Anne.Allen@neurosurgery.ufl.edu

Locations
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United States, Florida
McKnight Brain Institute of the University of Florida Recruiting
Gainesville, Florida, United States, 32611
Sponsors and Collaborators
University of Florida
Monteris Medical
Investigators
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Principal Investigator: Maryam Rahman, MD University of Florida
Principal Investigator: David Tran, PhD 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: February 7, 2020
Last Verified: February 2020
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
Additional relevant MeSH terms:
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Neoplasm Metastasis
Brain Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Bronchial Neoplasms
Carcinoma
Carcinoma, Renal Cell
Carcinoma, Non-Small-Cell Lung
Neoplastic Processes
Pathologic Processes
Adenocarcinoma
Kidney Diseases
Urologic Diseases
Central Nervous System Diseases
Nervous System Diseases
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Pembrolizumab