Lacosamide in Preventing Seizures in Participants With Malignant Glioma

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01432171
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 37
• Location: 1
• Arms: 2
• Actual Duration (Months): 58.8
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Glioma	Drug: Lacosamide; Other: Placebo	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. To determine if prophylactic administration of Lacosamide reduces the risk of seizures in patients with high-grade glioma (HGG).

SECONDARY OBJECTIVES:

1. To determine the one-year risk of first seizure in this patient population. II. To evaluate patient reported symptoms.

EXPLORATORY OBJECTIVES:

1. To investigate clinical and electroencephalographic predictors of seizures in this patient population.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 37 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Randomized, Double-Blind, Placebo-Controlled Trial of Lacosamide for Seizure Prophylaxis in Patients With High-Grade Gliomas
• Actual Study Start Date: Jul 25, 2012
• Actual Primary Completion Date: Jun 20, 2017
• Actual Study Completion Date: Jun 20, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (lacosamide) Participants receive lacosamide PO BID for up to 1 year. Treatment continues in the absence of disease progression or unacceptable toxicity.	Drug: Lacosamide; Given PO; Other Names: ADD 234037 Erlosamide Harkoseride SPM 927 Vimpat
Placebo Comparator: 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.	Other: Placebo; Given PO; Other Names: placebo therapy PLCB sham therapy

Outcome Measures

Primary Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Marta Penas-Prado, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 30, 2014

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01432171
• Other Study ID Numbers: BTTC11-01; NCI-2018-01854; BTTC11-01; P30CA016672
• First Posted: Sep 12, 2011
• Last Update Posted: Dec 19, 2018
• Last Verified: Nov 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glioma; Seizures; Lacosamide

Study Results

Participant Flow

Recruitment Details	Recruitment Period: July 25, 2012 to May 23, 2016. All recruitment done in medical clinical settings.

Arm/Group Title	Lacosamide (Vimpat)	Placebo
Arm/Group Description	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	Placebo orally twice a day.
Period Title: Overall Study
STARTED	18	19
COMPLETED	4	8
NOT COMPLETED	14	11

Baseline Characteristics

Arm/Group Title	Lacosamide	Placebo	Total
Arm/Group Description	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	Placebo orally twice a day.	Total of all reporting groups
Overall Participants	18	19	37
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	14 77.8%	15 78.9%	29 78.4%
>=65 years	4 22.2%	4 21.1%	8 21.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (12)	60 (10)	57 (11)
Sex: Female, Male (Count of Participants)
Female	6 33.3%	7 36.8%	13 35.1%
Male	12 66.7%	12 63.2%	24 64.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	18 100%	19 100%	37 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 11.1%	0 0%	2 5.4%
White	15 83.3%	18 94.7%	33 89.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 5.6%	1 5.3%	2 5.4%
Region of Enrollment (participants) [Number]
United States	18 100%	19 100%	37 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Seizures
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lacosamide	Placebo
Arm/Group Description	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	Placebo orally twice a day.
Measure Participants	18	19
Count of Participants [Participants]	0 0%	1 5.3%

Adverse Events

Time Frame	Adverse event data collected for up to one year treatment period.
Arm/Group Title	Lacosamide		Placebo
Arm/Group Description	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		Placebo orally twice a day.
All Cause Mortality
	Lacosamide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)		2/19 (10.5%)
Serious Adverse Events
	Lacosamide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/18 (11.1%)		6/19 (31.6%)
Gastrointestinal disorders
oral hemorrhage	0/18 (0%)	0	1/19 (5.3%)	1
abdominal pain	1/18 (5.6%)	1	0/19 (0%)	0
General disorders
gait disturbance	0/18 (0%)	0	1/19 (5.3%)	1
Infections and infestations
lung infection	0/18 (0%)	0	1/19 (5.3%)	1
infection, possible sepsis	0/18 (0%)	0	1/19 (5.3%)	1
Injury, poisoning and procedural complications
fall	1/18 (5.6%)	1	0/19 (0%)	0
Investigations
platelet count decreased	0/18 (0%)	0	2/19 (10.5%)	2
white blood cell count decreased	0/18 (0%)	0	2/19 (10.5%)	2
neutrophil count decreased	0/18 (0%)	0	1/19 (5.3%)	1
Metabolism and nutrition disorders
dehydration	1/18 (5.6%)	1	0/19 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
neoplasms benign, malignant	0/18 (0%)	0	1/19 (5.3%)	1
Nervous system disorders
headache	0/18 (0%)	0	1/19 (5.3%)	1
memory impairment	0/18 (0%)	0	1/19 (5.3%)	1
lethargy	1/18 (5.6%)	1	0/19 (0%)	0
seizure	0/18 (0%)	0	1/19 (5.3%)	1
Psychiatric disorders
confusion	1/18 (5.6%)	1	2/19 (10.5%)	2
hallucinations	0/18 (0%)	0	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
alopecia	0/18 (0%)	0	1/19 (5.3%)	1
Vascular disorders
thromboembolic event	1/18 (5.6%)	1	0/19 (0%)	0
hypotension	1/18 (5.6%)	1	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Lacosamide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/18 (88.9%)		17/19 (89.5%)
Blood and lymphatic system disorders
anemia	0/18 (0%)	0	1/19 (5.3%)	2
Eye disorders
eye disorders, other	0/18 (0%)	0	1/19 (5.3%)	2
Gastrointestinal disorders
constipation	0/18 (0%)	0	2/19 (10.5%)	2
gastroesophageal reflux disease	0/18 (0%)	0	2/19 (10.5%)	2
gastrointestinal disorders, other	0/18 (0%)	0	2/19 (10.5%)	2
General disorders
fatigue	2/18 (11.1%)	3	5/19 (26.3%)	5
gait disturbance	1/18 (5.6%)	2	2/19 (10.5%)	4
Infections and infestations
infections and infestations, other	2/18 (11.1%)	2	1/19 (5.3%)	1
Investigations
platelet count decreased	0/18 (0%)	0	2/19 (10.5%)	6
white blood cell decreased	0/18 (0%)	0	2/19 (10.5%)	8
alanine aminiotransferase increased	0/18 (0%)	0	2/19 (10.5%)	2
blood bilirubin increased	0/18 (0%)	0	1/19 (5.3%)	4
neutrophil count decreased	0/18 (0%)	0	1/19 (5.3%)	4
Musculoskeletal and connective tissue disorders
muscle weakness, left-sided	0/18 (0%)	0	3/19 (15.8%)	3
muscle weakness, right-sided	0/18 (0%)	0	2/19 (10.5%)	3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
neoplasms benigh, malignant and unspecified	1/18 (5.6%)	2	1/19 (5.3%)	1
Nervous system disorders
dyspnea	2/18 (11.1%)	2	0/19 (0%)	0
dysphasia	0/18 (0%)	0	2/19 (10.5%)	2
headache	4/18 (22.2%)	4	5/19 (26.3%)	5
memory impairment	0/18 (0%)	0	2/19 (10.5%)	2
seizure	0/18 (0%)	0	1/19 (5.3%)	1
Skin and subcutaneous tissue disorders
alopecia	0/18 (0%)	0	2/19 (10.5%)	2
Surgical and medical procedures
surgical and medical procedures	4/18 (22.2%)	6	0/19 (0%)	0
Vascular disorders
thromboembolic event	3/18 (16.7%)	3	2/19 (10.5%)	2
hypertension	0/18 (0%)	0	2/19 (10.5%)	3

Limitations/Caveats

This is a cooperative group protocol. It was not an MDACC protocol. BTTC was administratively located at MDACC. The main PI/Academic PI was located at an outside institution.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.