Phase 1-2 of Temozolomide and Hypofractionated Radiotherapy in Tx of Supratentorial Glioblastoma Multiform (Tx-Treatment)

Stanford University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Glioblastoma; Glioblastoma Multiforme; Cancer of Brain and Nervous System

Treatments: Drug: Temozolomide; Procedure: Stereotactic Radiosurgery (SRS)

Study type: Interventional

Funder types: Other

Identifiers

NCT01120639

SU-04202010-5726 (Other Identifier)

BRN0012 (Other Identifier)

IRB-17774 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to investigate the safety and effectiveness of a combination treatment for glioblastoma multiforme utilizing radiotherapy plus the FDA-approved chemotherapy drug temozolomide

Full description

Primary Objective: To determine the maximum tolerated dose (MTD), based on acute CNS toxicity at 30 days, of hypofractionated radiotherapy given in 5 fractions with temozolomide for the treatment of glioblastoma multiforme.

Secondary Objectives:

1. Assess the short- and long-term adverse effects.
2. Determine the radiographic response rate.
3. Determine the overall survival rate.
4. Assess quality of life during treatment

To determine the maximum tolerated dose (MTD) of hypofractionated (5 fractions) radiotherapy with temozolomide for the treatment of glioblastoma multiforme, patients will be evaluated by a multi-disciplinary team composed of radiation oncologists, neurosurgeons, and neuro-oncologists to assess for their eligibility. Patient's oncologic history, presenting symptoms, physical examination, pathology, and imaging studies will be reviewed. Patients will be evaluated for surgical candidacy and resectability. Patients who are surgical candidates will undergo a surgical resection prior to radiotherapy. Patients whose tumors are unresectable or are not good surgical candidates will undergo a biopsy for tissue diagnosis. Radiation will be delivered in five fractions.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histopathologically confirmed newly diagnosed glioblastoma multiforme. Diagnosis must be made by surgical biopsy or excision
• The tumor must be supratentorial in location
• The planning target volume (tumor plus margin) must measure ≤ 150 cm^3 in volume
• Age ≥ 18 years
• Life expectancy of at least 12 weeks
• Patient must have adequate organ function to tolerate temozolomide (details in the protocol)

Exclusion criteria

• Patients who have previously been treated with brain irradiation to the region that would result in overlap of the radiation fields
• Tumor foci detected below the tentorium
• Multifocal disease or leptomeningeal spread
• Prior allergic reaction to the study drugs involved in this protocol
• Patients with pacemaker will be allowed to undergo CT instead of MRI
• Pediatric patients (age < 18), pregnant women, and nursing patients will be excluded

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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30 participants in 4 patient groups

Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide

Experimental group

Description:

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Treatment:

Procedure: Stereotactic Radiosurgery (SRS)

Drug: Temozolomide

Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide

Experimental group

Description:

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Treatment:

Procedure: Stereotactic Radiosurgery (SRS)

Drug: Temozolomide

Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide

Experimental group

Description:

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Treatment:

Procedure: Stereotactic Radiosurgery (SRS)

Drug: Temozolomide

Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide

Experimental group

Description:

Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) \< 60 cm³ vs 60 to 150 cm³.

Treatment:

Procedure: Stereotactic Radiosurgery (SRS)

Drug: Temozolomide