| Eligibility |
Inclusion Criteria - Main Study Participants (Cohort 1) only
All participating subjects must meet the following criteria on the screening examination to
be eligible to participate in the study:
- Participants must be able to understand and willing to sign a written informed consent
document. The study requires authorization for collection, utilization and storage of
biological materials (blood, plasma, serum) to be used for research on the effects of
sBE on tissues.
- If the participant lives with a partner/spouse and they choose to participate in the
study as part of Cohort 2, the partner/spouse must be able to understand and be
willing to sign a written informed consent document. If the partner chooses not to
participate they will be given specific instructions for sleeping arrangements and not
being exposed to sBE therapy.
- Participants must allow the research team to assemble the sBE device in their homes
and conduct in-person visits or video conference calls for technical support.
Participants must reside within a 100 mile radius of Iowa City. Participants must
participate in in-person training of use of the sBE device and understand how to
safely use the sBE device, and agree to adhere to use only as instructed in the
instruction manual (see Appendix I).
- Participants must be able to adhere to using the sBE device daily for at least 8
hours, adhere to the scheduled visits, and agree to record sBE device usage hours
accurately and consistently in a daily diary.
- Participants must be 18 years of age or older on the day of signing the informed
consent document.
- Participants must have a Karnofsky Performance Status (KPS) = 60 (see Appendix B).
- Participants must be able to physically operate the sBE device independently or with
the assistance of a caretaker (see Appendix I).
- Participants must allow a collection of blood/plasma during scheduled visits where
labs will be collected for translational research study purposes.
- Participants must allow the study team to disassemble the sBE device and retrieve
static magnetic and electric generating components at the termination of the study.
Participants may keep the foam mattress or have it removed by the research team at the
time of sBE device disassembly.
- Patients must have histologically confirmed GBM (primary) with unequivocal first
progression of disease (confirmed by MRI or CT within 2 weeks of study registration).
- Patients must have previous history of failing temozolamide and radiation with this
being the first recurrence after standard of care therapy.
- Patients must have no history of bleeding diathesis, previous intracranial hemmorhage,
previous intolerance to lomustine or bevacizimab.
- If the patient has had surgical re-resection of the tumor, the following must be true:
- The surgery must confirm the recurrence, but residual or measurable disease after
surgery is not a requirement
- An MRI must be taken within 48-96 hours following the surgery
- Surgery must have been completed at least 2 weeks before starting treatment with
the sBE device
- Patients must have recovered from acute sequelae of surgery. When use of the sBE
device is initiated, the craniotomy or intracranial biopsy site must be adequately
healed as determined by:
- No drainage or cellulitis
- No residual sutures or staples
- Intact underlying cranioplasty (no craniectomy)
- Initiation of use with the sBE device must be > 2 weeks after the last tumor related
surgical procedure.
- If the patient is taking steroids, the dose must be stable or decreasing for at least
5 days before the baseline scan and up to the start of the study therapy.
- Absence of any recent hemorrhagic or thrombotic events in the brain.
Clinical labs - must be performed within 14 business days prior to registration and
determined to be within the reference ranges listed below:
- Hematology:
- Absolute neutrophil count (ANC) = 1.5 x 109 cells/L
- Platelet count = 100 x 109 cells/L
- Hemoglobin = 9.9 g/dL
- Biochemistry:
- Bilirubin < 1.5 x 1.2 mg/dL
- AST < 2.5 x 40 U/L (males) and < 2.5 x 32 U/L (females)
- ALT < 2.5 x 41 U/L (males) and < 2.5 x 33 U/L (females)
- ALP < 2.5 x 129 U/L (males) and < 2.5 x 104 (females)
- Plasma amylase = 1.5 x 100 U/L
- Plasma lipase = 1.5 x 60 U/L
- Creatinine < 1.5 x 1.2 mg/dL (males) and <1.5 x 1.0 mg/dL (females) or calculated
24 hour creatinine clearance = 50 mL/min
- Proteinuria (by urine dipstick) < 2. If = 2 proteinuria on dipstick urinalysis at
baseline, will need to undergo 24 hour urine collection and show = 1 g protein
within a 24 hour period.
- Total plasma calcium (corrected for plasma albumin as needed) or ionized calcium
within UIHC's reference range (8.6 - 10.3 mg/dL).
- Coagulation studies:
- INR < 1.5
- aPTT < 1.5 x 35 s, unless receiving therapeutic low molecular weight heparin
- Patients with a buffer range from the normal values of ± 5% for hematology and ± 10%
for biochemistry are acceptable as determined by the investigator.
Pregnancy and Reproduction
- Women of child-bearing potential (WOCBP) must agree to use a medical contraceptive
method during the treatment period and 6 months after the last dose of lomustine and
bevacizumab or with sBE device use, whichever is later. WOCBP include any female who
is not postmenopausal or has not undergone successful surgical sterilization
(bilateral tubal ligation, bilateral oophorectomy, or hysterectomy). Women must not be
breastfeeding. In general, appropriate methods of preventing pregnancy should be
discussed and agreed upon by the investigator and study participant.
- Acceptable contraception methods may include oral contraceptives, other hormonal
contraceptives (implants, an intrauterine device [IUD] or barrier method. If
condoms are used as a barrier method, a spermicidal agent should be added as a
double barrier protection.
- Post-menopause and not of child bearing potential is defined as 12 months of
natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with
plasma FSH levels > 40 mIU/mL and estradiol < 20 pg/mL.
- WOCBP must have a negative plasma or urine pregnancy test within 3 days prior to
starting treatment with the sBE device.
- Men must agree to use a reliable method of birth control and to not donate sperm
during the treatment period and for at least 6 months after the last dose of lomustine
and bevacizumab or treatment with the sBE device, whichever is later.
Exclusion Criteria
Participants who meet any of the following criteria will not be eligible for admission into
the study.
Previous Therapies
- Previous or current treatment with any investigational electromagnetic field
generating devices, including but not limited to the Optune and Voyager devices.
- Definitive radiation therapy within three months before the diagnosis of disease
progression. Palliative radiation 4 weeks prior to treatment is allowed.
Concomitant Medications & Devices
- Implanted electronic medical device including but not limited to implanted cardiac
defibrillator, pacemaker, deep brain stimulator.
- Patients who take enzyme-inducing anti-epileptic drugs (EIAED) must be put on
non-EIAED anti-convulsants at least 2 weeks prior to starting the lomustine and
bevacizumab.
- Underlying conditions that may interfere with lomustine, bevacizumab, or the
investigational sBE device within 6 months prior to study registration. If the medical
investigator feels intercurrent illness (ie. Infection) prevents delivery of lomustine
and bevacizumab they will be excluded.
- Current or recent use of anti-thrombotics or anti-coagulants including but not limited
to the following criteria:
- Use of aspirin > 325 mg/day or other NSAID with anti-platelet activity within 10
days of the first dose of bevacizumab
- Treatment with dipyramidole, ticlopidine, clopidogrel, or cilostaz within 10 days
of first dose of bevacizumab
- Use of full dose anti-coagulants if patient's international normalized ratio
(INR) > 1.5 x upper limit of the normal range (ULN) and activated prothrombin
time (aPTT) > 1.5 x ULN. Use of full dose anti-coagulants is permissible if the
INR or aPTT is within therapeutic limits according to the medical standards at
UIHC and the patient is stable on the current dose for at least 14 days before
starting investigational study.
Comorbidities
- History of known hypersensitivity to lomustine or bevacizumab formulations or
chemical/biological similars, recombinant human antibodies, humanized antibodies, or
Chinese hamster ovary cell products.
- Other previous malignancies, unless the patient was treated with curative intent > 2
years prior to registration and determined to be of low risk for recurrence as
determined by the treating investigator, with the exception of well controlled basal
cell carcinoma or squamous carcinoma of the skin or cervical cancer in situ.
- Hemorrhagic or thrombotic events within 6 months prior to study registration including
but not limited to history or evidence of inherited bleeding or coagulation disorders,
arterial or venous thromboses, history or evidence of stroke or TIAs, pulmonary
embolisms, or pulmonary hemorrhage/hemoptysis greater than grade 1 according to the
CTCAE v5.0 criteria within 1 month of study registration.
- Patients with any impairments in cardiac function within 6 months of the start of the
study or clinically significant cardiac diseases, including but not limited to MI,
severe/unstable angina, serious cardiac arrhythmias requiring medication or implanted
devices (e.g. pacemaker or ICD), second/third degree heart block, history of or
ongoing pericarditis, congestive heart failure (New York Heart Association functional
classification III-IV), cardiomyopathy, congenital long QT syndrome, coronary artery
bypass graft, aortic aneurysms requiring surgical intervention or peripheral arterial
thromboses, history of hypertensive crisis or hypertensive encephalopathy,
uncontrolled hypertension (defined by systolic BP > 150 mmHg and diastolic BP > 100
mmHg).
- Presence of an active or ongoing infection or serious underlying medical condition
including but not limited to chronic liver disease, chronic kidney disease, chronic
pulmonary disease, pancreatitis, or any other clinically relevant disease (other than
GBM) that in the investigator's opinion would interfere with the study.
- Psychosocial illness or situations that would interfere with participant compliance to
the study requirements.
- Any major systemic surgery = 2 weeks prior to the initiation of the study.
- Patients who are pregnant or breastfeeding.
- Patients with a history of known coagulopathy that increases risk of bleeding or a
history of clinically significant hemorrhage within 1 year of study registration.
SUBSTUDY PARTICIPANT SELECTION
The unaffected partner of the patient with recurrent GBM will be offered the option to
participate in the substudy of the feasibility and safety of treatment with a sBE device.
The unaffected partner must understand that their decision to participate or not
participate in the substudy is completely voluntary and does not in any way impact the
ability of their partner with rGBM to participate in the study. The same screening
examination and evaluation will be conducted for the unaffected partner as the patient with
recurrent GBM and are detailed in Section 10, Study Calendar. Within 2 weeks of
registration, all assessments will occur unless otherwise noted. Each substudy participant
must be fully informed on all aspects of the study for informed consent. If the unaffected
partner wishes to participate in the substudy, the written informed consent must be
obtained from the unaffected partner prior to enrollment of both the GBM patient and the
unaffected partner.
Following registration, any additional laboratory assessments and/or start of medication
that may alter tolerance to the prescribed combination of lomustine, bevacizumab and sBE
may be used to re-assess eligibility.
Inclusion Criteria - Substudy Participants (Cohort 2) only
All substudy participants must meet the following criteria on the screening examination to
be eligible to participate in the study:
- Able to understand and willing to sign a written informed consent document.
- Be the partner/spouse of a patient with rGBM and be cohabitating and sharing a bed
with said patient with rGBM.
- Agree to allow the research team to assemble the sBE device in their homes and conduct
in-person visits or video conference calls for technical support.
- Agree and be able to adhere to using the sBE device daily for at least 8 hours, adhere
to the scheduled visits, and agree to record the number of hours using the sBE device
accurately and consistently in a daily diary.
- Agree to getting a blood/plasma collection for translational research study purposes
at scheduled visits where blood collections are outlined.
- Agree to accompany their partner with rGBM to all clinical visits where feasibility
and safety assessments of the sBE device are being conducted.
- 18 years of age or older on the day of signing the informed consent document.
- Healthy as determined by screening assessment and the judgement of the principle
investigator.
- Able to physically operate the sBE device according to the provided instruction manual
(see Appendix I).
- Willing to end treatment with the sBE device when their partner with rGBM terminates
treatment with the sBE device.
- Willing to allow the study team to disassemble and retrieve the static magnetic and
electric generating components of the sBE device at the termination of the study.
- WOCBP must agree to use a medical contraceptive method during the 2-month period of
using the sBE device and 6 months after the treatment with the sBE device. WOCBP
include any female who is not postmenopausal or has not undergone successful surgical
sterilization (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy).
Women must not be breastfeeding. In general, appropriate methods of preventing
pregnancy should be discussed and agreed upon by the investigator and study
participant.
- Acceptable contraception methods may include oral contraceptives, other hormonal
contraceptives (implants, an intrauterine device [IUD] or barrier method. If condoms
are used as a barrier method, a spermicidal agent should be added as a double barrier
protection.
- Post-menopause and not of child bearing potential is defined as 12 months of
natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with
plasma FSH levels > 40 mIU/mL and estradiol < 20 pg/mL.
- WOCBP must have a negative plasma or urine pregnancy test within 3 days prior to
starting treatment with the sBE device.
- Men must agree to use a reliable method of birth control and to not donate sperm
during the treatment period and for at least 6 months after treatment with the sBE
device.
Exclusion Criteria
- Clinically relevant history or current presence of severe comorbidities as determined
by the principle investigator including but not limited to cardiovascular,
neurological, respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic,
or psychiatric diseases.
- Previous malignancies, unless the participant was treated with curative intent >2
years prior to registration or determined to be of low risk for recurrence by the
primary investigator, with the exception of well controlled basal cell carcinoma or
squamous carcinoma of the skin or cervical cancer in situ.
- Implanted electronic medical device including but not limited to implanted cardiac
defibrillator, pacemaker, deep brain stimulator
- Current or recent (within 4 weeks of before starting use of the sBE device) treatment
with any investigational drug(s) or device(s).
- History of seizures or current use of enzyme-inducing anti-epileptic drugs (EIAED).
- Any impairments in cardiac function within 6 months of the start of the study or
clinically significant cardiac diseases including but not limited to MI,
severe/unstable angina, serious cardiac arrhythmias requiring medication or implanted
devices (e.g. pacemaker or ICD), second/third degree heart block, history of or
ongoing pericarditis, congestive heart failure (New York Heart Association functional
classification III-IV), cardiomyopathy, congenital long QT syndrome, coronary artery
bypass graft, aortic aneurysms requiring surgical intervention or peripheral arterial
thromboses, history of hypertensive crisis or hypertensive encephalopathy,
uncontrolled hypertension (defined by systolic BP > 150 mmHg and diastolic BP > 100
mmHg).
- Presence of an active or ongoing infection or serious underlying medical condition
including but not limited to chronic liver disease, chronic kidney disease, chronic
pulmonary disease, pancreatitis, or any other clinically relevant disease that in the
investigator's opinion would interfere with the study.
- Psychosocial illness or situations that would interfere with participant compliance to
the study requirements.
- Any major systemic surgery =2 weeks prior to the initiation of the study.
- Pregnant or breastfeeding.
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