A Study Comparing GLIADEL to Stereotactic Radiosurgery in Metastatic Brain Disease

A Randomized Trial Evaluating GLIADEL Compared to Stereotactic Radiosurgery in Subjects With Metastatic Brain Disease

This study is being done to see if adding GLIADEL to the site where the tumor was removed works as well as just having the tumor removed with radiation treatment done within six weeks after the surgery to keep the cancer from coming back.

Study Overview

• Status: Recruiting
• Conditions: Brain Tumor - Metastatic
• Intervention / Treatment: Drug: Carmustine 7.7Mg Wafer

Detailed Description

This study is being done to assess the efficacy of GLIADEL (a local chemotherapy) in preventing local recurrence of a metastatic brain tumor compared to stereotactic radiosurgery (SRS) after resection.

100 Adult subjects with one to four metastatic brain tumors with one tumor needing resection will be enrolled. Subjects with prior radiation, lymphoma, small cell, germ cell, unknown primary, or anaplastic thyroid diagnoses will be ineligible. Life expectancy should be greater than 3 months.

Subjects will be randomized at the time of surgery to 1) GLIADEL placement at the time of resection or 2) SRS post-operatively to the resection cavity. Any other tumors (up to three) will have SRS as their primary treatment after surgery. SRS will take place within 6 weeks from surgery.

Subjects will be evaluated pre-operatively with MRI brain and neuropsychological testing and will have immediate post-op MRI for extent of resection (EOR) determination. Subjects will have SRS to the resection cavity if no GLIADEL was placed and all will have SRS to any other lesions. They will be followed at set intervals to evaluate for local recurrence and neurocognitive changes. The genome of the metastatic brain tumor will be compared to their primary and germline for identification of alterations.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Taylor A Johnson, BS, MA; Phone Number: 402-559-4596; Email: taylora.johnson@unmc.edu
• Study Contact Backup: Name: Erin E Rogers; Phone Number: 402-559-0963; Email: errogers@unmc.edu

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Not yet recruiting
      • Henry Ford
      • Principal Investigator: Ian Lee, MD
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska Medical Center
      • Contact: Michele R Aizenberg Ansari, MD; Phone Number: 402-559-9614; Email: maizenberg@unmc.edu
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Not yet recruiting
      • Ohio State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age 18 years or older (Nebraska is 19 years or older)
2. Karnofsky Performance Score ≥ 70
3. RPA class I or II
4. Known or suspected primary solid cancer with metastatic brain tumor(s) - up to four in number and up to 4 cm in size with surgical resection planned for one or two tumors.
5. Adequate platelet count (≥ 100,000/mm3), transfusion permitted
6. Laboratory values adequate for patient to undergo surgery, including: (transfusion permitted to reach goals)
7. Women of childbearing potential must have a negative pregnancy test within 7 days of initiating study
8. INR ≤ 1.3
9. Estimated survival time of ≥ 3 months as determined by the patient's primary oncologist.
10. The subject is willing and able to consent to and abide by the protocol.

Exclusion Criteria:

1. Prior treatment to the area of planned resection (surgery, radiation).
2. Prior whole brain radiation therapy.
3. Diagnosis of lymphoma, germ cell cancer, small cell lung cancer, anaplastic thyroid cancer.
4. Leptomeningeal disease
5. Neurodegenerative disorder (e.g. dementia).
6. Tumor size > 4 cm.
7. RPA class III
8. Inability or unwillingness to co-operate with the requirements of the protocol
9. Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or confound efficacy or safety assessment or a subject's ability to give informed consent.
10. Participation in other therapeutic clinical trials

11. Severe pulmonary, cardiac or other systemic disease, specifically:

    1. New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication
    2. Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia, clinically significant pulmonary disease
12. Subjects who have any other disease, either metabolic or psychological, which as per the Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications.
13. The subject has a bleeding diathesis, or must take anticoagulants, or antiplatelet agents including NSAIDs (non-steroidal anti-inflammatory drugs), at the time of scheduled resection that cannot be stopped for surgery.
14. Inability to obtain MRI studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard of Care Arm; The tumor will be removed surgically. Within 6 weeks after surgery, the resection will be treated with stereotactic radiosurgery (SRS).
Experimental: GLIADEL Arm; Once the tumor has been removed, GLIADEL wafers will be applied to the resection cavity. The number of wafers used will be determined by the size of the cavity. Enough wafers should be used so that as much of the cavity is covered as possible.	Drug: Carmustine 7.7Mg Wafer; GLIADEL wafers will be placed to cover tumor bed immediately after tumor removal.; Other Names: GLIADEL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of GLIADEL compared to Stereotactic Radiosurgery (SRS)	The primary outcome is to evaluate the efficacy of GLIADEL local chemotherapy compared to Stereotactic Radiosurgery (SRS) in preventing local recurrence after resection of a metastatic brain tumor (local recurrence at surgical site).	12 months

Collaborators and Investigators

• Sponsor: University of Nebraska
• Collaborators: Arbor Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Michele Aizenberg, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2020
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 6, 2020
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 9, 2020

Study Record Updates

• Last Update Posted (Actual): August 30, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Brain Diseases; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Carmustine
• Other Study ID Numbers: 0792-19-FB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No