Trial Outcomes & Findings for Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme (NCT NCT00544817)
NCT ID: NCT00544817
Last Updated: 2016-09-01
Results Overview
Defined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
47 participants
Primary outcome timeframe
18 months
Results posted on
2016-09-01
Participant Flow
Between April 2007 and July 2008, 47 patients were enrolled
Participant milestones
| Measure |
Combination Therapy
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
|
|---|---|
|
Combined Modality
STARTED
|
47
|
|
Combined Modality
COMPLETED
|
40
|
|
Combined Modality
NOT COMPLETED
|
7
|
|
No Treatment Interval
STARTED
|
40
|
|
No Treatment Interval
COMPLETED
|
28
|
|
No Treatment Interval
NOT COMPLETED
|
12
|
|
Follow-up Systemic Therapy
STARTED
|
28
|
|
Follow-up Systemic Therapy
COMPLETED
|
9
|
|
Follow-up Systemic Therapy
NOT COMPLETED
|
19
|
Reasons for withdrawal
| Measure |
Combination Therapy
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
|
|---|---|
|
Combined Modality
Lack of Efficacy
|
2
|
|
Combined Modality
Worsening Neurologic Symptoms
|
2
|
|
Combined Modality
Adverse Event
|
2
|
|
Combined Modality
Intercurrent Illness - Pneumonia
|
1
|
|
No Treatment Interval
Lack of Efficacy
|
8
|
|
No Treatment Interval
Physician Decision
|
3
|
|
No Treatment Interval
Adverse Event
|
1
|
|
Follow-up Systemic Therapy
Lack of Efficacy
|
15
|
|
Follow-up Systemic Therapy
Physician Decision
|
3
|
|
Follow-up Systemic Therapy
Intercurrent Illness - Pneumonia
|
1
|
Baseline Characteristics
Radiation Therapy and Temozolomide Followed by Temozolomide Plus Sorafenib for Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
Combination Therapy
n=47 Participants
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
|
|---|---|
|
Age, Continuous
|
54 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
47 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 18 monthsDefined as the duration of time from start of treatment to time of progression or death, whichever comes first.
Outcome measures
| Measure |
Combination Therapy
n=47 Participants
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
|
|---|---|
|
Progression-free Survival
|
6 Months
Interval 3.7 to 7.0
|
SECONDARY outcome
Timeframe: 18 monthsDefined as Day 1 of protocol treatment to date of death from any cause.
Outcome measures
| Measure |
Combination Therapy
n=47 Participants
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 Survival
|
12 Months
Interval 7.2 to 16.0
|
SECONDARY outcome
Timeframe: every 8 weeks until disease progression, estimated 18 monthsThe 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.
Outcome measures
| Measure |
Combination Therapy
n=47 Participants
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
|
|---|---|
|
Objective Response
|
13 participants
|
Adverse Events
Combination Therapy
Serious events: 19 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Combination Therapy
n=47 participants at risk
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
|
|---|---|
|
Gastrointestinal disorders
Diverticulitis
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Lung infection
|
2.1%
1/47 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Progressive disease
|
12.8%
6/47 • Number of events 6
|
|
Nervous system disorders
Acute radiation encephalopathy
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Dilantin toxicity
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.1%
1/47 • Number of events 2
|
|
Nervous system disorders
Seizure
|
4.3%
2/47 • Number of events 2
|
|
Nervous system disorders
Decreased LOC
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
DVT
|
2.1%
1/47 • Number of events 1
|
|
Blood and lymphatic system disorders
INR
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Urinary Tract Infection
|
2.1%
1/47 • Number of events 1
|
|
General disorders
Steroid-induced weakness
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Mental status changes
|
2.1%
1/47 • Number of events 1
|
|
Nervous system disorders
Speech impairment
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.1%
1/47 • Number of events 1
|
|
Vascular disorders
Bilateral pulmonary emboli
|
2.1%
1/47 • Number of events 1
|
|
Infections and infestations
Septicemia
|
2.1%
1/47 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
2.1%
1/47 • Number of events 1
|
|
Cardiac disorders
Cardiac ischemia/infarction
|
2.1%
1/47 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.1%
1/47 • Number of events 1
|
Other adverse events
| Measure |
Combination Therapy
n=47 participants at risk
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
|
|---|---|
|
Skin and subcutaneous tissue disorders
Rash - Hand-Foot Skin Reaction
|
21.3%
10/47 • Number of events 17
|
|
General disorders
Fatigue
|
68.1%
32/47 • Number of events 63
|
|
Skin and subcutaneous tissue disorders
Rash
|
42.6%
20/47 • Number of events 35
|
|
Gastrointestinal disorders
Nausea
|
44.7%
21/47 • Number of events 35
|
|
Gastrointestinal disorders
Diarrhea
|
23.4%
11/47 • Number of events 15
|
|
Gastrointestinal disorders
Vomiting
|
21.3%
10/47 • Number of events 13
|
|
Cardiac disorders
Hypertension
|
8.5%
4/47 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Hair loss/Alopecia
|
42.6%
20/47 • Number of events 37
|
|
Metabolism and nutrition disorders
ALT/SGPT
|
8.5%
4/47 • Number of events 8
|
|
Gastrointestinal disorders
Anorexia
|
38.3%
18/47 • Number of events 30
|
|
Metabolism and nutrition disorders
Bicarbonate serum-low
|
6.4%
3/47 • Number of events 3
|
|
Eye disorders
Vision - Blurred Vision
|
10.6%
5/47 • Number of events 5
|
|
Nervous system disorders
Confusion
|
36.2%
17/47 • Number of events 21
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.8%
6/47 • Number of events 6
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease Progression
|
12.8%
6/47 • Number of events 6
|
|
Nervous system disorders
Dizziness
|
10.6%
5/47 • Number of events 5
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
6.4%
3/47 • Number of events 4
|
|
Gastrointestinal disorders
Taste Alteration (dysgeusia)
|
12.8%
6/47 • Number of events 10
|
|
Gastrointestinal disorders
Dysphagia
|
6.4%
3/47 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.4%
3/47 • Number of events 4
|
|
Blood and lymphatic system disorders
Edema: Head and Neck
|
6.4%
3/47 • Number of events 4
|
|
Blood and lymphatic system disorders
Edema: Limb
|
14.9%
7/47 • Number of events 12
|
|
General disorders
Fever
|
6.4%
3/47 • Number of events 3
|
|
Blood and lymphatic system disorders
Hemoglobin
|
23.4%
11/47 • Number of events 15
|
|
Metabolism and nutrition disorders
Bilirubin (hyperbilirubinemia)
|
6.4%
3/47 • Number of events 5
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
21.3%
10/47 • Number of events 13
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
12.8%
6/47 • Number of events 6
|
|
Metabolism and nutrition disorders
Metablolic/Laboratory - Other (hypobilirubinemia)
|
6.4%
3/47 • Number of events 3
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
8.5%
4/47 • Number of events 4
|
|
Metabolism and nutrition disorders
Glucose, serum-low (hypoglycemia)
|
6.4%
3/47 • Number of events 3
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
10.6%
5/47 • Number of events 5
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
8.5%
4/47 • Number of events 4
|
|
Renal and urinary disorders
Incontinence, urinary
|
6.4%
3/47 • Number of events 3
|
|
Infections and infestations
Infection - Other, Lung (pneumonia)
|
6.4%
3/47 • Number of events 4
|
|
Renal and urinary disorders
Infection - Other, Urinary Tract NOS
|
8.5%
4/47 • Number of events 6
|
|
General disorders
Insomnia
|
14.9%
7/47 • Number of events 14
|
|
Blood and lymphatic system disorders
Leukocytes (total WBC)
|
27.7%
13/47 • Number of events 24
|
|
Nervous system disorders
Memory Impairment
|
8.5%
4/47 • Number of events 7
|
|
Nervous system disorders
Mood Alteration, Anxiety
|
14.9%
7/47 • Number of events 9
|
|
Nervous system disorders
Mood Alteration, Depression
|
14.9%
7/47 • Number of events 9
|
|
Gastrointestinal disorders
Mucositis
|
6.4%
3/47 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Muscle Weakness
|
25.5%
12/47 • Number of events 17
|
|
Nervous system disorders
Seizure
|
23.4%
11/47 • Number of events 12
|
|
Nervous system disorders
Neuropathy: Motor
|
19.1%
9/47 • Number of events 19
|
|
Nervous system disorders
Neuropathy: Sensory
|
6.4%
3/47 • Number of events 9
|
|
Blood and lymphatic system disorders
Neutrophils/granulocytes (ANC/AGC)
|
12.8%
6/47 • Number of events 6
|
|
Gastrointestinal disorders
Pain - Abdomen NOS
|
6.4%
3/47 • Number of events 3
|
|
Nervous system disorders
Pain - Headache
|
38.3%
18/47 • Number of events 24
|
|
Musculoskeletal and connective tissue disorders
Pain - Extremity-limb
|
8.5%
4/47 • Number of events 5
|
|
General disorders
Pain - Pain NOS
|
17.0%
8/47 • Number of events 11
|
|
Nervous system disorders
Personality/behavioral
|
10.6%
5/47 • Number of events 5
|
|
Blood and lymphatic system disorders
Platelets
|
34.0%
16/47 • Number of events 28
|
|
Nervous system disorders
Somnolence/depressed level of consciousness
|
12.8%
6/47 • Number of events 7
|
|
Nervous system disorders
Speech Impairment
|
23.4%
11/47 • Number of events 18
|
|
Nervous system disorders
Tremor
|
8.5%
4/47 • Number of events 4
|
|
General disorders
Weight Loss
|
10.6%
5/47 • Number of events 11
|
|
Gastrointestinal disorders
Constipation
|
21.3%
10/47 • Number of events 17
|
|
Musculoskeletal and connective tissue disorders
Erythema
|
6.4%
3/47 • Number of events 7
|
|
Infections and infestations
Infection - Thrush
|
8.5%
4/47 • Number of events 4
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER