Preoperative Chemoradiation for Glioblastoma

Phase I Pilot Study of Preoperative Chemoradiation for Glioblastoma

Trial to determine the safety of neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: Temozolomide; Radiation: partial brain irradiation; Procedure: stereotactic biopsy of brain tumor; Procedure: craniotomy and tumor resection

Detailed Description

Prior to any definitive treatment and after enrollment, the patient will undergo stereotactic biopsy of the lesion to confirm the histology of the lesion and to determine methylated methylguanine methyltransferase (MGMT) status. Standard image-guided stereotactic technique will be used. Patients will be treated with conformal radiation therapy. Temozolomide will be given from the day prior to radiation therapy through the last day of radiation therapy. 4-6 weeks after radiation therapy the patient will undergo craniotomy and maximal safe resection. Temozolomide will continue beginning 4 weeks after surgery.

Imaging:

MRI within 2 weeks prior to the start of the protocol. MRI at 4 weeks after chemoradiation therapy and prior to surgery. MRI within 48 hours after surgery.

MRI after every 2 cycles of chemotherapy and then every 2 months until progression, up to 2 years.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• MRI lesions of the brain that have a high probability of being glioblastoma in a potentially resectable location in the brain (the primary study population)
• WHO performance status 0-2 (to allow comparison to historical controls)
• Adequate hematological parameters: (for safety because of neutropenia from the temozolomide)
• Consent can be obtained from the patient, and if the patient cannot give consent then from the medical power of attorney and if one is not assigned, then the nearest relative (required to obtain consent)
• Able to have MRI scans (secondary endpoint is MRI scan characteristics)
• Willing to have radiation treatment at a participating center (homogeneity of treatment parameters)
• Ages 18-80

Exclusion Criteria:

• Unresectable tumor
• Absolute neutrophil count (ANC) less than 1,200/μL
• Hemoglobin less than 9.0g/dL
• Platelet count less than 100,000/μL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Preoperative chemoradiation; Stereotactic biopsy of brain tumor, then partial brain irradiation and temozolomide, followed by craniotomy and tumor resection, followed by temozolomide

Drug: Temozolomide; Neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.; Other Names: Temodar; Radiation: partial brain irradiation; Neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.; Procedure: stereotactic biopsy of brain tumor; will be assessed for tumor type and tumor markers; Procedure: craniotomy and tumor resection; maximal safe resection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
toxicity of treatment per Common Toxicity Criteria for Adverse Effects V3.0	comparison of toxicity related to experimental treatment to historical local controls	up to up to 16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of measurement of O(6)-Methylguanine-DNA methyltransferase (MGMT) activity on stereotactic samples	determination of the feasibility of using standard MGMT activity measurement techniques on stereotactic specimens and comparison of the results with the results from the full resection.	at enrollment
progression free survival		up to 12 months
overall survival		up to 12 months

Collaborators and Investigators

• Sponsor: Tampa General Hospital
• Investigators: Principal Investigator: Lawrence Berk, MD, PhD, Tampa General Hospital

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: March 11, 2014
• First Submitted That Met QC Criteria: March 17, 2014
• First Posted (ESTIMATE): March 19, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): November 10, 2015
• Last Update Submitted That Met QC Criteria: November 7, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: neoadjuvant; radiotherapy; surgery; radiation therapy; glioblastoma; temozolomide; pre-operative
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Temozolomide
• Other Study ID Numbers: TGH0001