Clinical Trials /

LITT and Pembrolizumab in Recurrent Brain Metastasis

NCT04187872

Description:

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).

Related Conditions:
  • Cancer
  • Cervical Carcinoma
  • Classical Hodgkin Lymphoma
  • Esophageal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • Mediastinal Large B-Cell Lymphoma
  • Melanoma
  • Merkel Cell Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Small Cell Lung Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: LITT and Pembrolizumab in Recurrent Brain Metastasis
  • Official Title: Recurrent Brain Metastasis Immune Effects and RespOnse to Laser Interstitial ThermotHerapy (LITT) and Pembrolizumab in Combination (TORCH)

Clinical Trial IDs

  • ORG STUDY ID: IRB201902411
  • SECONDARY ID: OCR26353
  • NCT ID: NCT04187872

Conditions

  • Melanoma
  • Non-small Cell Lung Carcinoma (NSCLC)
  • Renal Cell Carcinoma (RCC)
  • Brain Metastases

Purpose

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).

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.
    

Trial Arms

NameTypeDescriptionInterventions
Patients with Recurrent Brain MetastesExperimentalAdult 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.

    Eligibility 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).
          
    Maximum Eligible Age:100 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Immune Effect of LITT plus pembrolizumab
    Time Frame:From first dose pembro through 30 days after administration of pembro
    Safety Issue:
    Description: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

    Measure:Safety and tolerability of LITT plus pembrolizumab
    Time Frame:From first dose pembro to 30 days post final pembro dose
    Safety Issue:
    Description:Adverse events will be collected for each patient from the first dose of pembrolizumab until end of the study treatment.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:University of Florida

    Last Updated

    December 3, 2019