Human stem cell derived neuron
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A Pilot Study of an Implantable Microdevice for In Situ Evaluation of Drug Response in Patients with Primary Brain Tumors

Summary

This pilot study will assess the feasibility of using an implantable microdevice to measure local intratumor response to chemotherapy, immunotherapy, and other clinically relevant drugs in gliomas. The microdevice is about the size of a grain of rice and contains multiple reservoirs each loaded with a specific drug that is released in microdoses into distinct regions of tumor. It will be implanted within a tumor at the time of stereotactic biopsy and allowed to remain within the tumor tissue for approximately 72 hours. During the tumor resection, the device will be removed along with tissue from the insertion site for genomic analysis.

The goals of this feasibility study are to assess the practical application of a microdevice for testing drug sensitivity in the clinical setting and to acquire preliminary data regarding whether local response to microdoses of specific drugs may be predictive or prognostic in glioma.

Inclusion Criteria
  1. Written informed consent (and assent, when applicable), obtained from subject or subject legal representative, and ability for the subject to comply with the requirements of the study.
  2. Patients must have operable supratentorial tumor presumed to be WHO grade 2-4 glioma based on radiological evidence at MRI, where a gross total or partial surgical resection is intended.
  3. Histological confirmation of WHO grade 2-4 glioma at time of intraoperative frozen analysis (for newly diagnosed tumors). For recurrent tumors, evidence of viable tumor will need to be confirmed by frozen section analysis.
  4. Participants must be 18 years of age or older.
  5. Karnofsky Performance Score ≥ 60.
  6. Participants must have normal organ and marrow function as defined below:
    1. Leukocytes ≥ 3,000/mcL
    2. Absolute neutrophil count ≥ 1,500/mcL
    3. Platelets ≥ 100,000/mcL
    4. Total bilirubin within normal institutional limits
    5. AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
    6. Creatine within normal institutional limits OR
    7. Creatine clearance ≥ 60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
  7. 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.
  8. Because participants will be exposed to microdoses of therapeutic agents only in a localized setting, 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.
  9. 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
  10. Ability to understand and the willingness to sign a written informed consent document.
  11. Patients who are receiving systemic therapies for their tumor, including  those contained in the microdevice, are still eligible for the trial, as long as microdevice implantation does not happen before 5 half-lives have passed from the last systemic administration.
Exclusion Criteria
  1. Participants who have received anti VEGF therapy within 4 weeks before the time of planned microdevice insertion.
  2. Participants who have received radiotherapy to the brain within 12 weeks before  the time of planned microdevice insertion.
  3. Participants who are within 5 half-lives of treatment using one or multiple agents contained by the device.
  4. History of allergic reactions attributed to compounds of similar chemical or biologic composition to the microdevice or any agents used in the study.
  5. 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.
  6. 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.
  7. Tumor located in eloquent (e.g. motor cortex) or deep brain structures (e.g. thalamus, brainstem).
  8. Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical procedures.
  9. 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.
Investigator(s)

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