Clinical Trials /

Implantable Microdevice In Primary Brain Tumors

NCT04135807

Description:

This pilot study will assess the safety and feasibility of using an implantable microdevice to measure local intratumor response to chemotherapy and other clinically relevant drugs in malignant brain tumors. - The device involved in this study is called a microdevice. - The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

Related Conditions:
  • Anaplastic Astrocytoma
  • Anaplastic Oligodendroglioma
  • Astrocytoma
  • Glioblastoma
  • Malignant Supratentorial Neoplasm
  • Oligodendroglioma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Implantable Microdevice In Primary Brain Tumors
  • Official Title: A Pilot Study of an Implantable Microdevice for In Situ Evaluation of Drug Response in Patients With Primary Brain Tumors

Clinical Trial IDs

  • ORG STUDY ID: 18-623
  • NCT ID: NCT04135807

Conditions

  • Grade II Glioma
  • Grade III Glioma
  • Grade IV Glioma
  • Astrocytoma
  • Oligodendroglioma of Brain
  • Anaplastic Astrocytoma of Brain
  • Anaplastic Oligodendroglioma
  • Glioblastoma

Purpose

This pilot study will assess the safety and feasibility of using an implantable microdevice to measure local intratumor response to chemotherapy and other clinically relevant drugs in malignant brain tumors. - The device involved in this study is called a microdevice. - The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

Detailed Description

      This research study is a Pilot Study, which is the first time investigators are examining
      this study device in brain tumors.

      The FDA (the U.S. Food and Drug Administration) has not approved the microdevice as a
      treatment for any disease.

      Investigators are studying the safety of the microdevice and the effects of different drugs
      for each specific tumor. Brain tumors are known to be very different from each other and
      respond differently to different drugs. It would be very helpful to find out what drugs have
      the best chance of working in each specific tumor.

      This research study involves drugs that are released by a small device, as small as the tip
      of a needle, that is inserted into the tumor at the time of surgery and is removed at the end
      of the surgery. The goal of this research study is to prove that microdevices can be used to
      find out which drugs have better effects on treating malignant brain tumors.

      Participants will be in this research study for up to 30 days.

      Expected enrollment is about 12 people.
    

Trial Arms

NameTypeDescriptionInterventions
MicrodeviceExperimentalThe research study procedures include screening for eligibility and study treatment including evaluations and follow up visits. Patients with newly found supratentorial lesions, or patients previously diagnosed with supratentorial gliomas at time of recurrence, whose treatment plan includes partial or total resection surgery as a component of standard-of-care treatment will be included. - Placement of 1-3 microdevices (depending on the size of the tumor) before tumor resection is started. -- The microdevices will dwell in the tumor tissue for a time window of 2-4 hours to allow time for tissue effects of the drugs microdoses for intratumor release of the following 8 approved drugs: Temozolomide, Lomustine, Irinotecan, Carboplatin, Lapatinib, Osimertinib, Abenaciclib, and Everolimus. The drugs used in this study will only include drugs already used systemically for the treatment of gliomas.

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Patients must have operable supratentorial tumor presumed to be WHO grade II-IV glioma
                 (Astrocytoma, Oligodendroglioma, Anaplastic Astrocytoma, Anaplastic Oligodendroglioma,
                 or Glioblastoma) based on radiological evidence at MRI, where a gross total or partial
                 surgical resection is intended.
    
              -  Histological confirmation of WHO grade II-IV glioma at time of intraoperative frozen
                 analysis (for newly diagnosed tumors). This is not necessary in cases where a
                 histopathologic diagnosis is already available from prior surgeries/biopsies.
    
              -  Participants must be 18 years of age or older.
    
              -  Karnofsky Performance Score ≥ 60 (Appendix C).
    
              -  Participants must have normal organ and marrow function as defined below:
    
                   -  Leukocytes ≥ 3,000/mcL
    
                   -  Absolute neutrophil count ≥ 1,500/mcL
    
                   -  Platelets ≥ 100,000/mcL
    
                   -  Total bilirubin within normal institutional limits
    
                   -  AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
    
                   -  Creatinine within normal institutional limits OR
    
                   -  Creatinine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels
                      above institutional normal.
    
              -  Participants must be evaluated by a neurosurgeon who will determine the feasibility of
                 microdevice implantation based on clinical history, extent, and anatomical location of
                 the tumor.
    
              -  Because participants will be exposed to microdoses of therapeutic agents only in a
                 localized setting and for a short period of time (2-4 hours), the risk of interaction
                 with other drugs routinely assumed by participants is considered not applicable. Thus,
                 participants receiving any medications or substances that are inhibitors or inducers
                 of CYP450 enzymes remain eligible.
    
              -  The effects of the microdevice on the developing human fetus are unknown. For this
                 reason and because the therapeutic agents used in this trial are known to be
                 teratogenic, women of child-bearing potential must agree to have a negative serum
                 pregnancy test within 48 hours prior to registration. Women of child-bearing potential
                 and men must agree to use adequate contraception (hormonal or barrier method of birth
                 control; abstinence) prior to study entry and for the duration of study participation.
                 Should a woman become pregnant or suspect she is pregnant while she or her partner is
                 participating in this study, she should inform her treating physician immediately. Men
                 treated or enrolled on this protocol must also agree to use adequate contraception
                 prior to the study and for the duration of study participation.
    
              -  Ability to understand and the willingness to sign a written informed consent document.
    
            Exclusion Criteria:
    
              -  Participants who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
                 nitrosoureas) prior to entering the study or those who have not recovered from adverse
                 events due to agents administered more than 4 weeks earlier.
    
              -  Participants who are receiving any other investigational agents.
    
              -  History of allergic reactions attributed to compounds of similar chemical or biologic
                 composition to the microdevice or any agents used in the study.
    
              -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
                 infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
                 arrhythmia, or psychiatric illness/social situations that would limit compliance with
                 study requirements.
    
              -  Pregnant women are excluded from this study because agents released by the microdevice
                 have the potential for teratogenic or abortifacient effects. Because there is an
                 unknown but potential risk for adverse events in nursing infants secondary to
                 treatment of the mother with the agents used in this study, breastfeeding should be
                 discontinued if the mother is treated in the study for a total of 14 days after
                 removal of the microdevice.
    
              -  Tumor size < 5 cm3.
    
              -  Tumor located in deep brain structures (e.g. thalamus, brainstem).
    
              -  Uncorrectable bleeding or coagulation disorder known to cause increased risk with
                 surgical procedures.
    
              -  If there are significant risk factors (e.g. high risk of venous thrombosis, pulmonary
                 embolism, stroke or myocardial infarction) precluding the safe cessation of
                 anticoagulation medication as per SIR guidelines, patients will be excluded from the
                 trial.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Success Rate of Microdevice Retrieval
    Time Frame:1 day
    Safety Issue:
    Description:Defined as the ability to retrieve the microdevice with sufficient tissue, of sufficient quality, for downstream histopathology analysis and interpretation of at least 50% of the microdevice reservoirs.

    Secondary Outcome Measures

    Measure:Measure Local Intratumor Response to Different Agents
    Time Frame:1 Day
    Safety Issue:
    Description:two-tailed alpha level of 0.05 and report 95% confidence intervals with any point estimates
    Measure:Correlate Tissue Genetic Features with Drug Response
    Time Frame:1 Day
    Safety Issue:
    Description:Preliminary correlations between a specific genetic feature and drug response will be tested using the Chi-squared/Fisher's exact test for categorical variables or the T-test or Wilcoxon Rank-Sum test for continuous variables.

    Details

    Phase:Early Phase 1
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Oliver Jonas

    Trial Keywords

    • Grade II Glioma
    • Grade III Glioma
    • Grade IV Glioma
    • Astrocytoma
    • Oligodendroglioma of Brain
    • Anaplastic Astrocytoma of Brain
    • Glioblastoma

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