Implantable Microdevice for the Evaluation of Drug Response in Patients with Primary Brain Tumors
- Patients must have operable supratentorial tumor presumed to be World Health Organization (WHO) grade II-IV glioma (astrocytoma, oligodendroglioma, anaplastic astrocytoma, anaplastic oligodendroglioma, or glioblastoma) based on radiological evidence at magnetic resonance imaging (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
- Karnofsky performance score >= 60
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance >= 60 mL/min/1.73 m^2 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
- 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 cm^3
- 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 Society of Interventional Radiology (SIR) guidelines, patients will be excluded from the trial
I. To determine the feasibility of microdevice analysis based on the ability to place and retrieve the device with sufficient tissue, of sufficient quality, for downstream histopathology and molecular analysis of at least 50% of the implanted device reservoirs.
II. To determine the safety of the microdevice implantation and removal procedure.
I. To determine and quantify the biological effect of different drugs within the same tumor specimen.
II. To compare the biological effect of microdevices in an in situ setting against the effects observed in a tumor-matched mouse model.
Patients undergo placement of 1-3 microdevices to receive standard of care drugs (temozolomide, lomustine, irinotecan hydrochloride, carboplatin, lapatinib ditosylate, osimertinib, abemaciclib, and everolimus) over 2-4 hours during standard of care tumor resection. Patients then have the microdevices removed before the end of surgery.
After completion of study, patients are followed up for 30 days.
Trial Phase Phase O
Trial Type Diagnostic
Dana-Farber Harvard Cancer Center
Pier Paolo Peruzzi
- Primary ID 18-623
- Secondary IDs NCI-2020-01989
- Clinicaltrials.gov ID NCT04135807