Validation of the Role of Levetiracetam for Newly Diagnosed GBM Patients

June 23, 2016 updated by: Chae-Yong Kim, Seoul National University Hospital

The Prospective Trial for Validation of the Role of Levetiracetam as a Sensitizer of Temozolomide in the Treatment of Newly Diagnosed Glioblastoma Patients

Prospective, open-labeled, multicenter cohort trial for validation of the role of levetiracetam as a sensitizer of temozolomide in the treatment of newly diagnosed glioblastoma patients.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

I. Objectives

<Primary Endpoint>

6 months progression-free survival (6m-PFS)

<Secondary Endpoint>

  1. Overall survival
  2. Safety (adverse events)
  3. Quality of life using EORTC module,
  4. Cognitive function using NOPT module of our institution

<Explorative Endpoint>

Genetic biomarker for predicting prognosis

  1. Methylation status of MGMT promoter
  2. IDH mutation
  3. TERT mutation / ATRX status

II. Hypothesis

1.Proof of concept

  • With using of levetiracetam, there will be an improved survival with chemoradiotherapy with temozolomide compared to the group without using levetiracetam. (superiority) 2. Safety
  • It will be tolerable in this concept. 3. Genetic biomarker
  • Methylation status of MGMT, IDH1 mutation, TERT mutation, and ATRX status will prove to be valid molecular markers of prognostic significance in newly diagnosed glioblastoma treated with the combination of levetiracetam.

III. Study Design/Clinical Plan

  1. Group I (prospective)

    • Patients in this group are with newly diagnosed glioblastoma patients who are supposed to be treated with concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide (TMZ). Patients in Group I will be given levetiracetam (LEV) from the beginning of treatment till after the adjuvant chemotherapy with TMZ is over.
  2. Group II (historical group; using data base from KSNO multicenter study group)

IV. Treatment

  1. Levetiracetam: started with 250mg bid and is increased up to 500mg bid in perioperative period. During the 2 days of peri-operation, it is administered in intravenous form mixed in 150ml of normal saline. After immediate postoperative period, 500~1500mg bid is administered in per oral form according to patient's clinical condition. During the period of adjuvant chemotherapy with temozolomide, the dose not less than 500mg is administered unless there are serious side effects of levetiracetam.
  2. Temozolomide based standard treatment: CCRT with temozolomide followed by 6cycles of adjuvant temozolomide RT with daily temozolomide (75 mg/m2/day, 7 days/week) from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg/m2 for 5 days during each 28-day cycle).

V. Evaluation

MR scans were performed before the first adjuvant treatment cycle and then every 3 months during the first year, and every 4 months during the second year. Radiographic response is determined in comparison to the tumor measurement obtained at pretreatment baseline measurements as a reference and is categorized into four groups using new criteria proposed by the Response Assessment in Neuro-Oncology (RANO) working group.

VI. Statistical Plans

Total sample size: 73 The size of sample is considered by assessment of PFS. The number of event and statistical power was calculated on assumption of exponential distribution of the 7 months median PFS in the control group and 12 months median PFS in the treatment group.

The expected sample size provides 80% of test power that can perceive 1.7 of hazard ration with 0.05 of type I error in comparative analysis of PFS at the time of 12 months of registering period (in equal entry pattern) and at 6 months of follow up period. Basis on this assumption, it is expected that 73 patients are needed in the treatment group, and 74 patients in the control group.

Study Type

Interventional

Enrollment (Anticipated)

73

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Newly diagnosed histologically proven supratentorial glioblastoma (World Health Organization [WHO] Grade IV). The histological diagnosis must be obtained from a neurosurgical resection or biopsy of a tumor including an open biopsy or stereotactic biopsy.
  2. Age 20 -76 years
  3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2

  4. Meets 1 of the following RPA classifications:

    4-1. Class III (Age <50 years and ECOG PS 0) 4-2. Class IV (meeting one of the following criteria: a) Age <50 years and ECOG PS 1 or b) Age ≥50 years, underwent prior partial or total tumor resection, MMSE ≥27) 4-3. Class V (meeting one of the following criteria: a) Age ≥50 years and underwent prior partial or total tumor resection, MMSE <27 or b) Age ≥50 years and underwent prior tumor biopsy only)

  5. Adequate hematologic, renal, and hepatic function:

    ANC > 1,500/uL Platelet > 100,000/uL Serum creatinine <1.7mg/dL Bilirubin level < 2.0 mg/dL AST/ALT < 2.5 x upper limit of normal range of each institution

  6. Written informed consent

Exclusion Criteria:

  1. Prior chemotherapy within last 5 years
  2. Prior radiotherapy of the head and neck area
  3. Receiving concurrent investigational agents or has received an investigational agent within 30 days prior to randomization
  4. Planned surgery for other diseases (e.g. dental extraction)
  5. History of malignancy. Subjects with curatively treated cervical carcinoma in situ or basal cell carcinoma of the skin, or subjects who have been free of other malignancies for 5 years are eligible for this study
  6. Pregnant or lactating women
  7. Subject who disagree to follow acceptable methods of contraception
  8. Concurrent illness including unstable heart disease despite appropriate treatment, history of myocardial infarction within 6 months, serious neurological or psychological disease, and uncontrolled infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Levetiracetam
Newly diagnosed histologically proven supratentorial glioblastoma patients received levetiracetam during and after their CCRT
Drug: levetiracetam
Patients in this group are with newly diagnosed glioblastoma patients who are supposed to be treated with concurrent chemoradiotherapy (CCRT) and adjuvant chemotherapy with temozolomide (TMZ). Patients ( intervention Group) will be given levetiracetam (LEV) from the beginning of treatment till after the adjuvant chemotherapy with TMZ is over.
Other Names:
  • keppra®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
6 months Progression free survival
Time Frame: from the first operation to following 6 months
from the first operation to following 6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: from the first operation to following 36 months
from the first operation to following 36 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Seoul National University Hospital

Investigators

  • Principal Investigator: Chae-Yong Kim, PhD, Seoul National University Bundang Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2016

Primary Completion (Anticipated)

June 1, 2019

Study Completion (Anticipated)

June 1, 2022

Study Registration Dates

First Submitted

June 14, 2016

First Submitted That Met QC Criteria

June 23, 2016

First Posted (Estimate)

June 28, 2016

Study Record Updates

Last Update Posted (Estimate)

June 28, 2016

Last Update Submitted That Met QC Criteria

June 23, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • cykim

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Glioblastoma Multiforme

Clinical Trials on levetiracetam

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Russia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe