Implantable microdevice to test drug effects in primary brain tumors

A Pilot Study of an Implantable Microdevice for In Situ Evaluation of Drug Response in Patients With Primary Brain Tumors

A tiny implantable device is placed into your glioma during surgery to see if local releases of standard glioma drugs cause tumor responses.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Brigham and Women's Hospital (other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT04135807 on ClinicalTrials.gov

What this trial studies

This pilot early-phase study places a small microdevice into operable supratentorial WHO grade II–IV gliomas at the time of resection to deliver minute, localized doses of drugs already used systemically for gliomas. The device is removed at the end of the surgery and adjacent tumor tissue is examined for signs of drug effect. The study will enroll about 12 participants and follow safety and feasibility outcomes for up to 30 days. The aim is to determine whether the device can reliably measure intratumoral drug response and be safely used in brain tumors.

Who should consider this trial

Good fit: Adults (≥18 years) with operable supratentorial WHO grade II–IV gliomas planned for surgical resection, Karnofsky Performance Score ≥60, and adequate organ and marrow function are the intended candidates.

Not a fit: Patients with inoperable tumors, non-glioma histology, significant organ dysfunction, or those not undergoing resection are unlikely to receive benefit from this implant-based approach.

Why it matters

Potential benefit: If successful, the device could help identify which approved drugs are most active against an individual patient's tumor, supporting more personalized treatment choices.

How similar studies have performed: Similar implantable microdevice approaches have shown early promise in other solid tumors, but this is the first pilot testing the device specifically in brain tumors.

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.

Where this trial is running

Boston, Massachusetts

• Brigham and Women's Hospital — Boston, Massachusetts, United States (RECRUITING)

Study contacts

• Principal investigator: Pier Paolo Peruzzi, MD, PhD — Brigham and Women's Hospital
• Study coordinator: Pier Paolo Peruzzi, MD, PhD

Conditions: Grade II Glioma, Grade III Glioma, Grade IV Glioma, Astrocytoma, Oligodendroglioma of Brain, Anaplastic Astrocytoma of Brain, Anaplastic Oligodendroglioma, Glioblastoma