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

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01120639
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 4
• Duration (Months): 127.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma; Cancer of Brain and Nervous System; Glioblastoma Multiforme	Drug: Temozolomide; Procedure: Stereotactic Radiosurgery (SRS)	Phase 1/Phase 2

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Dose-escalation with 2-level stratificationDose-escalation with 2-level stratification
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1-2 Trial of Temozolomide and Hypofractionated Radiotherapy in Treatment of Supratentorial Glioblastoma Multiforme
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 15, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stereotactic Radiosurgery (25 Gray x 5 fractions)+Temozolomide Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.	Drug: Temozolomide; 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.; Other Names: Temodar Temodal ; Procedure: Stereotactic Radiosurgery (SRS); Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy); Other Names: Hypofractionated stereotactic radiosurgery (h-SRS) Hypofractionated stereotactic radiotherapy Cyberknife surgery
Experimental: Stereotactic Radiosurgery (30 Gray x 5 fractions)+Temozolomide Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.	Drug: Temozolomide; 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.; Other Names: Temodar Temodal ; Procedure: Stereotactic Radiosurgery (SRS); Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy); Other Names: Hypofractionated stereotactic radiosurgery (h-SRS) Hypofractionated stereotactic radiotherapy Cyberknife surgery
Experimental: Stereotactic Radiosurgery (35 Gray x 5 fractions)+Temozolomide Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.	Drug: Temozolomide; 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.; Other Names: Temodar Temodal ; Procedure: Stereotactic Radiosurgery (SRS); Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy); Other Names: Hypofractionated stereotactic radiosurgery (h-SRS) Hypofractionated stereotactic radiotherapy Cyberknife surgery
Experimental: Stereotactic Radiosurgery (40 Gray x 5 fractions)+Temozolomide Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³.	Drug: Temozolomide; 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy.; Other Names: Temodar Temodal ; Procedure: Stereotactic Radiosurgery (SRS); Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy); Other Names: Hypofractionated stereotactic radiosurgery (h-SRS) Hypofractionated stereotactic radiotherapy Cyberknife surgery

Outcome Measures

Primary Outcome Measures

1. Number of Dose-limiting Toxicities (DLTs) [30 days]

   The maximum-tolerated dose (MTD) of study treatment (temozolomid plus hypofractionated radiotherapy administered as 5 fractions) is defined as either: The highest radiation dose per protocol, or The radiation dose at which dose-limiting toxicities (DLTs) occurred in ≥ 2 of 3 participants at a dose level, and/or ≥ 2 of 6 participants, at a dose level. Dose-limiting toxicity (DLT) was defined as a treatment-related (with possible, probable or definite attribution) Grade 3 to 5 CNS toxicity [Common Terminology Criteria for Adverse Events (CTCAE) v4] occurring within 30 days of stereotactic radiosurgery (SRS). The non-stratified outcome is reported as the number of DLTs observed in by radiation dose and by strata (Planning Target Volume (PTV) < 60 cm³ and from 60 to 150 cm³).

Secondary Outcome Measures

1. Number of Acute Toxicity Within 30 Days [30 days]

   Acute toxicity is defined as treatment-related adverse events that occur within 30 days of receiving radiotherapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is used to grade adverse events. The non-stratified outcome is reported as number of treatment-related adverse events observed for each radiotherapy dose level. Acute toxicity is based on radiotherapy dose level not tumor volume, and is reported by radiotherapy dose level only.

2. Long-term Toxicity After More Than 30 Days [12 months]

   Long-term toxicity is defined as treatment-related adverse events (any grade or any Body System) that occur ≥ 30 days after receiving radiotherapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is used to grade adverse events. The non-stratified outcome is reported as number of treatment-related adverse events observed for each dose level. Long-term toxicity is based on radiotherapy dose level not tumor volume, and is reported by radiotherapy dose level only.

3. Percent of Participants With Radiographic Response [6 months]

   Radiographic response rate was assessed following radiotherapy until disease progression. Response is considered to be the sum and proportion participants that achieved a complete response (CR); partial response (PR); or minor response (MR). The outcome is expressed as a number without dispersion for each cohort. CR: Tumor is no longer detected by computed tomography (CT) or magnetic resonance imaging (MRI). PR: Decrease in the product of the two greatest diameters > 50%, as determined by CT or MRI, with no new lesions, and the same or lower dose of dexamethasone. MR: Decrease in the product of the two greatest diameters < 50%, as determined by CT or MRI, and neither PR nor PD. PD: New tumor lesion, or > 25% increase in the product of the two greatest diameters of target lesion, as determined by CT or MRI, provided that within 2 months of completion of radiotherapy, the participant has not had a decrease in steroid dose since the last evaluation.

4. Progression-free Survival [18 Months.]

   Progression-free survival (PFS) following radiotherapy, measured in months. Progressive disease (PD) is defined as: New tumor lesion, or > 25% increase in the product of the 2 greatest diameters of target lesion, as determined by computed tomography (CT) or magnetic resonance imaging (MRI), provided that within 2 months of completion of radiotherapy, the participant has not had a decrease in steroid dose since the last evaluation. The outcome is expressed as the median with 95% confidence interval for each cohort.

5. Overall Survival (OS) [20 Months.]

   Overall survival (OS) was assessed as those participants remaining alive with any tumor status following radiotherapy after 20 months. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and expressed as the median value with 95% confidence interval.

6. Quality of Life by European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30) Survey [12 Months]

   European Organization for Research and Treatment of Cancer (EORTC-QLQ C30) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). The EORTC-QLQ C30 survey has 30 questions and responses are on scale of 1 to 4 with 1 indicating "not at all" and 4 indicating "very much". The total score can range from 30 to 120. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and is expressed as the mean of the difference from baseline to 12 months, with 95% confidence interval.

7. Quality of Life by Brain-20 Survey [12 months]

   Brain-20 (BN-20) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). The Brain-20 (BN-20) quality of life survey has 20 questions and responses are on scale of 1 to 4 with 1 indicating "not at all" (most favorable) and 4 indicating "very much" (least favorable). The total score can range from 20 to 80, and the result is expressed as the difference from baseline (study entry) to 12 months after the start of treatment. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and expressed as the mean with 95% confidence interval.

8. Quality of Life by MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Survey [12 months]

   MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). MDASI-BT quality of life survey has 23 questions and responses are on scale of 0 to 10 with 0 indicating "did not interfere" (most favorable) and 10 indicating "interfered completely" (least favorable). A participant's overall score is computed as the mean of that participant's individual scores, and can range 0 to 10. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and expressed as the mean difference from baseline with 95% confidence interval. A positive value for the mean indicates worsening quality of life.

9. Treatment Failure Analysis [18 months]

   Treatment failure in individual participants, ie, tumor recurrence or metastasis, can be described by the location relative to the first treatment failure (ie, infield, marginal, or distal), as further defined below. Failure pattern is defined as tumor recurrence or metastasis relative to the primary lesion that is Infield: at tumor or within 5 mm Marginal: > 5 mm or ≤ 20 mm from tumor Distal: > 20 mm from tumor The outcome will be reported as the number of participants who failed treatment for each type of failure, ie, infield, marginal, or distal failure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University

Investigators

• Principal Investigator: Scott Gerard Soltys, MD, Stanford University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 3, 2015

More Information

Publications

None provided.

• Responsible Party: Scott Soltys, Assistant Professor of Radiation Oncology, Stanford University
• ClinicalTrials.gov Identifier: NCT01120639
• Other Study ID Numbers: IRB-17774; SU-04202010-5726; BRN0012; IRB-17774
• First Posted: May 11, 2010
• Last Update Posted: Aug 6, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Glioblastoma; Brain Neoplasms; Temozolomide

Study Results

Participant Flow

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Period Title: Overall Study
STARTED	6	6	6	12
COMPLETED	6	6	6	12
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide	Total
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Total of all reporting groups
Overall Participants	6	6	6	12	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 33.3%	4 66.7%	3 50%	5 41.7%	14 46.7%
>=65 years	4 66.7%	2 33.3%	3 50%	7 58.3%	16 53.3%
Age (Years) [Median (Standard Deviation) ]
Median (Standard Deviation) [Years]	72 (5.8)	61.4 (8.3)	62.8 (10.0)	67.1 (8.6)	65.9 (8.5)
Sex: Female, Male (Count of Participants)
Female	4 66.7%	3 50%	4 66.7%	4 33.3%	15 50%
Male	2 33.3%	3 50%	2 33.3%	8 66.7%	15 50%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	6 100%	12 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Dose-limiting Toxicities (DLTs)
Description	The maximum-tolerated dose (MTD) of study treatment (temozolomid plus hypofractionated radiotherapy administered as 5 fractions) is defined as either: The highest radiation dose per protocol, or The radiation dose at which dose-limiting toxicities (DLTs) occurred in ≥ 2 of 3 participants at a dose level, and/or ≥ 2 of 6 participants, at a dose level. Dose-limiting toxicity (DLT) was defined as a treatment-related (with possible, probable or definite attribution) Grade 3 to 5 CNS toxicity [Common Terminology Criteria for Adverse Events (CTCAE) v4] occurring within 30 days of stereotactic radiosurgery (SRS). The non-stratified outcome is reported as the number of DLTs observed in by radiation dose and by strata (Planning Target Volume (PTV) < 60 cm³ and from 60 to 150 cm³).
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

Participants receiving each radiotherapy level were stratified by tumor size.

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	6	6	6	12
Planning Target Volume (PTV) < 60 cm³	0	0	0	1
Planning Target Volume (PTV) 60 to 150 cm³	0	0	0	1

2. Secondary Outcome

Title	Number of Acute Toxicity Within 30 Days
Description	Acute toxicity is defined as treatment-related adverse events that occur within 30 days of receiving radiotherapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is used to grade adverse events. The non-stratified outcome is reported as number of treatment-related adverse events observed for each radiotherapy dose level. Acute toxicity is based on radiotherapy dose level not tumor volume, and is reported by radiotherapy dose level only.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	6	6	6	12
CTCAE Grade 1	5	2	2	4
CTCAE Grade 2	0	0	1	0
CTCAE Grade 3	0	0	1	0
CTCAE Grade 4	0	0	0	1
CTCAE Grade 5	0	0	0	1
All grades	5	2	4	6

3. Secondary Outcome

Title	Long-term Toxicity After More Than 30 Days
Description	Long-term toxicity is defined as treatment-related adverse events (any grade or any Body System) that occur ≥ 30 days after receiving radiotherapy. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0 is used to grade adverse events. The non-stratified outcome is reported as number of treatment-related adverse events observed for each dose level. Long-term toxicity is based on radiotherapy dose level not tumor volume, and is reported by radiotherapy dose level only.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	6	6	6	12
CTCAE Grade 1	0	0	1	1
CTCAE Grade 2	0	1	1	1
CTCAE Grade 3	3	4	1	3
CTCAE Grade 4	0	0	0	1
All grades	3	5	3	6

4. Secondary Outcome

Title	Percent of Participants With Radiographic Response
Description	Radiographic response rate was assessed following radiotherapy until disease progression. Response is considered to be the sum and proportion participants that achieved a complete response (CR); partial response (PR); or minor response (MR). The outcome is expressed as a number without dispersion for each cohort. CR: Tumor is no longer detected by computed tomography (CT) or magnetic resonance imaging (MRI). PR: Decrease in the product of the two greatest diameters > 50%, as determined by CT or MRI, with no new lesions, and the same or lower dose of dexamethasone. MR: Decrease in the product of the two greatest diameters < 50%, as determined by CT or MRI, and neither PR nor PD. PD: New tumor lesion, or > 25% increase in the product of the two greatest diameters of target lesion, as determined by CT or MRI, provided that within 2 months of completion of radiotherapy, the participant has not had a decrease in steroid dose since the last evaluation.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	6	6	6	12
Planning Target Volume (PTV) <60 CM3	100 1666.7%	100 1666.7%	100 1666.7%	33.3 277.5%
Planning Target Volume (PTV) 60-150CM3	66.7 1111.7%	66.7 1111.7%	66.7 1111.7%	16.7 139.2%

5. Secondary Outcome

Title	Progression-free Survival
Description	Progression-free survival (PFS) following radiotherapy, measured in months. Progressive disease (PD) is defined as: New tumor lesion, or > 25% increase in the product of the 2 greatest diameters of target lesion, as determined by computed tomography (CT) or magnetic resonance imaging (MRI), provided that within 2 months of completion of radiotherapy, the participant has not had a decrease in steroid dose since the last evaluation. The outcome is expressed as the median with 95% confidence interval for each cohort.
Time Frame	18 Months.

Outcome Measure Data

Analysis Population Description

Participants who have not progresses and have not reached reached 18 months post-treatment are not included.

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	3	3	3	6
Planning Target Volume (PTV) <60 CM3	13.4	10.5	33.5	3.9
Planning Target Volume (PTV) 60-150CM3	7.2	6.5	8.8	4.0

6. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival (OS) was assessed as those participants remaining alive with any tumor status following radiotherapy after 20 months. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and expressed as the median value with 95% confidence interval.
Time Frame	20 Months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	3	3	3	6
Planning Target Volume (PTV) <60 CM3	17.6	19.9	48.3	10.2
Planning Target Volume (PTV) 60-150CM3	10.1	11.3	17.6	11.6

7. Secondary Outcome

Title	Quality of Life by European Organisation for Research and Treatment of Cancer (EORTC-QLQ C30) Survey
Description	European Organization for Research and Treatment of Cancer (EORTC-QLQ C30) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). The EORTC-QLQ C30 survey has 30 questions and responses are on scale of 1 to 4 with 1 indicating "not at all" and 4 indicating "very much". The total score can range from 30 to 120. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and is expressed as the mean of the difference from baseline to 12 months, with 95% confidence interval.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Some participants did not contribute one or both of the baseline (study entry) and 12-month assessments, and the outcome (difference from baseline / study entry to 12 months after the start of treatment could not be calculated.

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	5	6	6	11
Planning Target Volume (PTV) <60 CM3	41.6	58.3	80.5	53.3
Planning Target Volume (PTV) 60-150CM3	41.6	52.7	44.4	51.3

8. Secondary Outcome

Title	Quality of Life by Brain-20 Survey
Description	Brain-20 (BN-20) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). The Brain-20 (BN-20) quality of life survey has 20 questions and responses are on scale of 1 to 4 with 1 indicating "not at all" (most favorable) and 4 indicating "very much" (least favorable). The total score can range from 20 to 80, and the result is expressed as the difference from baseline (study entry) to 12 months after the start of treatment. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and expressed as the mean with 95% confidence interval.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Some participants did not contribute one or both of the baseline (study entry) and 12-month assessments, and the outcome (difference from baseline / study entry to 12 months after the start of treatment could not be calculated.

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	5	6	6	11
Planning Target Volume (PTV) <60 CM3	66.6	40.7	18.5	44.4
Planning Target Volume (PTV) 60-150CM3	40.7	55.5	59.2	25.9

9. Secondary Outcome

Title	Quality of Life by MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Survey
Description	MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) quality of life surveys were administered at study entry and 12 months after treatment initiation to assess health-related quality of life (HR-QOL). MDASI-BT quality of life survey has 23 questions and responses are on scale of 0 to 10 with 0 indicating "did not interfere" (most favorable) and 10 indicating "interfered completely" (least favorable). A participant's overall score is computed as the mean of that participant's individual scores, and can range 0 to 10. The outcome is stratified by Planning Target Volume (PTV) < 60 cm³ or 60 to 150 cm³, and expressed as the mean difference from baseline with 95% confidence interval. A positive value for the mean indicates worsening quality of life.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Some participants did not contribute one or both of the baseline (study entry) and 12-month assessments, and the outcome (difference from baseline / study entry to 12 months after the start of treatment could not be calculated.

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	4	5	6	11
Planning Target Volume (PTV) <60 CM3	5.2	2.0	2.8	3.2
Planning Target Volume (PTV) 60-150CM3	3.7	3.2	2.3	3.6

10. Secondary Outcome

Title	Treatment Failure Analysis
Description	Treatment failure in individual participants, ie, tumor recurrence or metastasis, can be described by the location relative to the first treatment failure (ie, infield, marginal, or distal), as further defined below. Failure pattern is defined as tumor recurrence or metastasis relative to the primary lesion that is Infield: at tumor or within 5 mm Marginal: > 5 mm or ≤ 20 mm from tumor Distal: > 20 mm from tumor The outcome will be reported as the number of participants who failed treatment for each type of failure, ie, infield, marginal, or distal failure.
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

If the location of a participant's 1st treatment failure could not be determined, then a location assessment relative to any 2nd treatment failure can not done (null result), and for this reason, this analysis only includes participants for whom the location of the 1st treatment failure could be determined.

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide	Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
Measure Participants	6	6	4	11
In-Field	2 33.3%	5 83.3%	2 33.3%	8 66.7%
Marginal	1 16.7%	0 0%	1 16.7%	1 8.3%
Distal	3 50%	1 16.7%	1 16.7%	2 16.7%

Adverse Events

Arm/Group Title	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
Arm/Group Description	Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)		Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)		Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)		Hypofractionated stereotactic radiosurgery with concurrent temozolomide, stratified by Planning Target Volume (PTV) < 60 cm³ vs 60 to 150 cm³. Temozolomide: 75 mg/m²/day oral, administered concurrently with radiotherapy and as adjuvant therapy. Stereotactic Radiosurgery (SRS): Standard of care therapeutic radiotherapy administrated at 25, 30, 35, or 40 Gray (Gy)
All Cause Mortality
	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		5/6 (83.3%)		4/6 (66.7%)		10/12 (83.3%)
Serious Adverse Events
	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		6/6 (100%)		0/6 (0%)		9/12 (75%)
Infections and infestations
Urinary tract infection	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, death	4/6 (66.7%)	4	1/6 (16.7%)	1	0/6 (0%)	0	2/12 (16.7%)	2
Nervous system disorders
Nervous system disorders-Other, altered mental state	1/6 (16.7%)	1	2/6 (33.3%)	2	0/6 (0%)	0	0/12 (0%)	0
Seizure	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	3/12 (25%)	3
Edema cerebral	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders - Other, pulmonary embolism	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Surgical and medical procedures
Surgical and medical procedures - Other, ressection of recurrent tumor	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/12 (0%)	0
Vascular disorders
Thromboembolic event	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Stereotactic Radiosurgery (25 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (30 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (35 Gray x 5 Fractions)+Temozolomide		Stereotactic Radiosurgery (40 Gray x 5 Fractions)+Temozolomide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/6 (100%)		5/6 (83.3%)		6/6 (100%)		12/12 (100%)
General disorders
Fatigue	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	3/12 (25%)	3
Nervous system disorders
Headache	3/6 (50%)	3	0/6 (0%)	0	1/6 (16.7%)	1	2/12 (16.7%)	2
Nervous system disorders -Other, necrosis	1/6 (16.7%)	1	1/6 (16.7%)	1	4/6 (66.7%)	4	2/12 (16.7%)	2
Nervous system disorders -Other, aphasia	0/6 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	1/12 (8.3%)	1
Syncope	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/12 (0%)	0
Amnesia	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0
Tremor	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/12 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	3/6 (50%)	3	2/6 (33.3%)	2	2/6 (33.3%)	2	4/12 (33.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.