Malignant Glioma
Conditions
Brief summary
This trial studies how well lacosamide works in preventing seizures in participants with malignant glioma. Anti-seizure drugs, such as lacosamide, may decrease abnormal electrical activity in the brain that plays a role in developing seizures.
Detailed description
PRIMARY OBJECTIVES: I. To determine if prophylactic administration of Lacosamide reduces the risk of seizures in patients with high-grade glioma (HGG). SECONDARY OBJECTIVES: I. To determine the one-year risk of first seizure in this patient population. II. To evaluate patient reported symptoms. EXPLORATORY OBJECTIVES: I. To investigate clinical and electroencephalographic predictors of seizures in this patient population. II. To evaluate the occurrence of symptoms and correlate to seizure activity as well as tolerance to treatment using the MD Anderson Symptom Inventory-Brain Tumor Module (MDASI-BT) self-reporting tool. OUTLINE: Participants are randomized to 1 of 2 arms. ARM I (LACOSAMIDE): Participants receive lacosamide orally (PO) twice a day (BID) for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity. ARM II (PLACEBO): Participants receive a placebo PO BID for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up every 3 months for 5 years.
Interventions
DRUGLacosamide
Given PO
OTHERPlacebo
Given PO
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with histologically confirmed supratentorial high-grade glioma will be eligible for this protocol. * All patients must sign an informed consent indicating that they are aware of the investigational nature of this study. * Patients must have signed an authorization for the release of their protected health information. * Patients must have a Karnofsky performance status of \>= 60. * Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 2 weeks prior to registration. * In the opinion of the treating investigator, patients must have adequate cognitive abilities to complete the neurocognitive components of the study. * Patients must be able to safely swallow pills. * Patients must agree to practice adequate contraception. * Patients must be registered on study within 16 weeks after the surgical procedure that established the diagnosis of high grade glioma.
Exclusion criteria
* Patients must not have any significant medical or psychiatric illnesses that in the investigator's opinion cannot be adequately controlled with appropriate therapy or would compromise the patient's ability to tolerate this therapy. * Patients must not have serious intercurrent medical illness. Serious, active co-morbidity, defined as follows: a) Unstable angina and/or congestive heart failure requiring hospitalization within the last 12 months. b) Transmural myocardial infarction within the last 6 months. c) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration. d) Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration. e) Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects; note, however, that laboratory tests for liver function and coagulation parameters are not required for entry into this protocol. f) Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. g) Active connective tissue disorders, such as lupus or scleroderma, that in the opinion of the treating physician may put the patient at high risk for radiation toxicity. * Patients must not be pregnant or breast feeding. Patients must not be pregnant because lacosamide produced developmental toxicity in rats following administration during pregnancy. There is insufficient information to determine if lacosamide is safe during lactation. * Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism. * Patients must not have a history of heart block or cardiac arrhythmia, including asymptomatic arrhythmias and atrial fibrillation/flutter. * Patients must not have a prolonged PR interval (defined as \> 200 ms). * Perioperative anticonvulsants should be tapered as indicated in the protocol. * Patients must not have a history of any type of seizure for at least 10 years prior to registration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Seizures | 12 months or first seizure | Number of Participants that had seizure in a randomized, two-arm, parallel groups of post-operative participants with newly-diagnosed high-grade glioma (HGG) |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: July 25, 2012 to May 23, 2016. All recruitment done in medical clinical settings.
Participants by arm
| Arm | Count |
|---|---|
| Lacosamide Lacosamide orally twice a day, starting dose 50 mg with dose escalation (increased by 100 mg/day weekly) until target dose 200 mg achieved over 4 weeks | 18 |
| Placebo Placebo orally twice a day. | 19 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 2 |
| Overall Study | Insurance denial trial coverage | 1 | 0 |
| Overall Study | Lost to Follow-up | 6 | 5 |
| Overall Study | Noncompliance | 2 | 3 |
| Overall Study | Patient moved to palliative care | 1 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Lacosamide | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 15 Participants | 29 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 12 | 60 years STANDARD_DEVIATION 10 | 57 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 18 Participants | 19 Participants | 37 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 15 Participants | 18 Participants | 33 Participants |
| Region of Enrollment United States | 18 participants | 19 participants | 37 participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Male | 12 Participants | 12 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 18 | 2 / 19 |
| other Total, other adverse events | 16 / 18 | 17 / 19 |
| serious Total, serious adverse events | 2 / 18 | 6 / 19 |
Outcome results
Primary
Number of Participants With Seizures
Number of Participants that had seizure in a randomized, two-arm, parallel groups of post-operative participants with newly-diagnosed high-grade glioma (HGG)
Time frame: 12 months or first seizure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Lacosamide | Number of Participants With Seizures | 0 Participants |
| Placebo | Number of Participants With Seizures | 1 Participants |