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Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00544817
Recruitment Status : Completed
First Posted : October 16, 2007
Results First Posted : December 13, 2012
Last Update Posted : September 1, 2016
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
SCRI Development Innovations, LLC

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioblastoma Multiforme
Interventions Radiation: Radiation Therapy
Drug: Temozolomide
Drug: Sorafenib
Enrollment 47
Recruitment Details Between April 2007 and July 2008, 47 patients were enrolled
Pre-assignment Details  
Arm/Group Title Combination Therapy
Hide Arm/Group Description

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

Period Title: Combined Modality
Started 47
Completed 40
Not Completed 7
Reason Not Completed
Lack of Efficacy             2
Worsening Neurologic Symptoms             2
Adverse Event             2
Intercurrent Illness - Pneumonia             1
Period Title: No Treatment Interval
Started 40
Completed 28
Not Completed 12
Reason Not Completed
Lack of Efficacy             8
Physician Decision             3
Adverse Event             1
Period Title: Follow-up Systemic Therapy
Started 28
Completed 9
Not Completed 19
Reason Not Completed
Lack of Efficacy             15
Physician Decision             3
Intercurrent Illness - Pneumonia             1
Arm/Group Title Combination Therapy
Hide Arm/Group Description

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

Overall Number of Baseline Participants 47
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 47 participants
54
(28 to 79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants
Female
16
  34.0%
Male
31
  66.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 47 participants
47
1.Primary Outcome
Title Progression-free Survival
Hide Description Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy
Hide Arm/Group Description:

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

Overall Number of Participants Analyzed 47
Median (95% Confidence Interval)
Unit of Measure: Months
6
(3.7 to 7)
2.Secondary Outcome
Title Overall Survival
Hide Description Defined as Day 1 of protocol treatment to date of death from any cause.
Time Frame 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy
Hide Arm/Group Description:

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

Overall Number of Participants Analyzed 47
Median (95% Confidence Interval)
Unit of Measure: Months
12
(7.2 to 16)
3.Secondary Outcome
Title Objective Response
Hide Description

The number of patients with complete or partial responses measured from the time of initial response to documented tumor progression. Radiologic response was defined using the Macdonald criteria.

The Macdonald criteria divides response into 4 types of response based on imaging (MRI) and clinical features, as follows: 1) complete response (CR); 2) partial response (PR); 3) stable disease (SD); and 4) progression (PD).

Criteria:

CR: disappearance of all enhancing disease (measurable and non-measurable) sustained for at least 4 weeks, no new lesions. No corticosteroids, clinically stable or improved.

PR: >=50% decrease of all measurable enhancing lesions, sustained for at least 4 weeks, no new lesions. Stable or reduced corticosteroids, clinically stable or improved.

SD: does not qualify for complete response, partial response or progression. Clinically stable.

PD: >= 25% increase in enhancing lesions, any new lesions. Clinical deterioration.

Time Frame every 8 weeks until disease progression, estimated 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Combination Therapy
Hide Arm/Group Description:

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

Overall Number of Participants Analyzed 47
Measure Type: Number
Unit of Measure: participants
13
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Combination Therapy
Hide Arm/Group Description

In the combined modality portion of the study, patients were administered:

Radiation Therapy - 2 Gy/fraction, Single daily fractions M-F, to 60 Gy total Temozolomide - 75 mg/m2 by mouth once daily

Patients took a four week break before beginning follow-up systemic therapy:

Temozolomide - 150 mg /m2 by mouth on days 1-5 every 28 days for 6 cycles Sorafenib - 400 mg by mouth twice a day for 6 months

All-Cause Mortality
Combination Therapy
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
Combination Therapy
Affected / at Risk (%) # Events
Total   19/47 (40.43%)    
Blood and lymphatic system disorders   
Thrombocytopenia  1  1/47 (2.13%)  2
Leukopenia  1  1/47 (2.13%)  1
INR  1  1/47 (2.13%)  1
Cardiac disorders   
Cardiac ischemia/infarction  1  1/47 (2.13%)  1
Gastrointestinal disorders   
Diverticulitis  1  1/47 (2.13%)  1
General disorders   
Steroid-induced weakness  1  1/47 (2.13%)  1
Infections and infestations   
Lung infection  1  1/47 (2.13%)  1
Urinary Tract Infection  1  1/47 (2.13%)  1
Septicemia  1  1/47 (2.13%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Progressive disease  1  6/47 (12.77%)  6
Nervous system disorders   
Acute radiation encephalopathy  1  1/47 (2.13%)  1
Dilantin toxicity  1  1/47 (2.13%)  1
Seizure  1  2/47 (4.26%)  2
Decreased LOC  1  1/47 (2.13%)  1
Mental status changes  1  1/47 (2.13%)  1
Speech impairment  1  1/47 (2.13%)  1
Respiratory, thoracic and mediastinal disorders   
Respiratory failure  1  1/47 (2.13%)  1
Adult respiratory distress syndrome  1  1/47 (2.13%)  1
Skin and subcutaneous tissue disorders   
Rash  1  1/47 (2.13%)  1
Vascular disorders   
DVT  1  1/47 (2.13%)  1
Bilateral pulmonary emboli  1  1/47 (2.13%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination Therapy
Affected / at Risk (%) # Events
Total   32/47 (68.09%)    
Blood and lymphatic system disorders   
Edema: Head and Neck  1 [1]  3/47 (6.38%)  4
Edema: Limb  1  7/47 (14.89%)  12
Hemoglobin  1  11/47 (23.40%)  15
Leukocytes (total WBC)  1  13/47 (27.66%)  24
Neutrophils/granulocytes (ANC/AGC)  1  6/47 (12.77%)  6
Platelets  1  16/47 (34.04%)  28
Cardiac disorders   
Hypertension  1  4/47 (8.51%)  5
Eye disorders   
Vision - Blurred Vision  1  5/47 (10.64%)  5
Gastrointestinal disorders   
Nausea  1  21/47 (44.68%)  35
Diarrhea  1  11/47 (23.40%)  15
Vomiting  1  10/47 (21.28%)  13
Anorexia  1  18/47 (38.30%)  30
Taste Alteration (dysgeusia)  1  6/47 (12.77%)  10
Dysphagia  1  3/47 (6.38%)  7
Mucositis  1  3/47 (6.38%)  5
Pain - Abdomen NOS  1  3/47 (6.38%)  3
Constipation  1  10/47 (21.28%)  17
General disorders   
Fatigue  1  32/47 (68.09%)  63
Fever  1  3/47 (6.38%)  3
Insomnia  1  7/47 (14.89%)  14
Pain - Pain NOS  1  8/47 (17.02%)  11
Weight Loss  1  5/47 (10.64%)  11
Infections and infestations   
Infection - Other, Lung (pneumonia)  1  3/47 (6.38%)  4
Infection - Thrush  1  4/47 (8.51%)  4
Metabolism and nutrition disorders   
ALT/SGPT  1  4/47 (8.51%)  8
Bicarbonate serum-low  1  3/47 (6.38%)  3
Bilirubin (hyperbilirubinemia)  1  3/47 (6.38%)  5
Glucose, serum-high (hyperglycemia)  1  10/47 (21.28%)  13
Albumin, serum-low (hypoalbuminemia)  1  6/47 (12.77%)  6
Metablolic/Laboratory - Other (hypobilirubinemia)  1  3/47 (6.38%)  3
Calcium, serum-low (hypocalcemia)  1  4/47 (8.51%)  4
Glucose, serum-low (hypoglycemia)  1  3/47 (6.38%)  3
Potassium, serum-low (hypokalemia)  1  5/47 (10.64%)  5
Sodium, serum-low (hyponatremia)  1  4/47 (8.51%)  4
Musculoskeletal and connective tissue disorders   
Muscle Weakness  1  12/47 (25.53%)  17
Pain - Extremity-limb  1  4/47 (8.51%)  5
Erythema  1  3/47 (6.38%)  7
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Disease Progression  1  6/47 (12.77%)  6
Nervous system disorders   
Confusion  1  17/47 (36.17%)  21
Dizziness  1  5/47 (10.64%)  5
Memory Impairment  1  4/47 (8.51%)  7
Mood Alteration, Anxiety  1  7/47 (14.89%)  9
Mood Alteration, Depression  1  7/47 (14.89%)  9
Seizure  1  11/47 (23.40%)  12
Neuropathy: Motor  1  9/47 (19.15%)  19
Neuropathy: Sensory  1  3/47 (6.38%)  9
Pain - Headache  1  18/47 (38.30%)  24
Personality/behavioral  1  5/47 (10.64%)  5
Somnolence/depressed level of consciousness  1  6/47 (12.77%)  7
Speech Impairment  1  11/47 (23.40%)  18
Tremor  1  4/47 (8.51%)  4
Renal and urinary disorders   
Incontinence, urinary  1  3/47 (6.38%)  3
Infection - Other, Urinary Tract NOS  1  4/47 (8.51%)  6
Respiratory, thoracic and mediastinal disorders   
Cough  1  6/47 (12.77%)  6
Dyspnea  1  3/47 (6.38%)  4
Skin and subcutaneous tissue disorders   
Rash - Hand-Foot Skin Reaction  1  10/47 (21.28%)  17
Rash  1  20/47 (42.55%)  35
Hair loss/Alopecia  1  20/47 (42.55%)  37
Dry Skin  1  3/47 (6.38%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Face
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The sponsor can review/embargo results communications prior to public release for a period that is >60 days but ≤180 days from date submitted to sponsor, who may require changes to the communication in order to remove specifically identified confidential information (other than study data) and/or delay the proposed publication to enable the sponsor to seek patent protection for inventions. The PI may not publish its results until 18 mos. after the trial has been completed at all sites.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: John D. Hainsworth, MD
Organization: Sarah Cannon Research Institute
Phone: 877-691-7274
EMail: ASKSARAH@scresearch.net
Layout table for additonal information
Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00544817    
Other Study ID Numbers: SCRI CNS 09
First Submitted: October 15, 2007
First Posted: October 16, 2007
Results First Submitted: November 15, 2012
Results First Posted: December 13, 2012
Last Update Posted: September 1, 2016