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.
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.
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.
