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Trial record 85 of 107 for:    PHENYTOIN

Tamoxifen and Bortezomib to Treat Recurrent Brain Tumors

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: NCT00108069
Recruitment Status : Completed
First Posted : April 13, 2005
Results First Posted : June 12, 2014
Last Update Posted : November 5, 2015
Sponsor:
Information provided by (Responsible Party):
Katherine E. Warren, M.D., National Institutes of Health Clinical Center (CC)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Glioma
Interventions Drug: Tamoxifen citrate
Drug: Bortezomib
Enrollment 43
Recruitment Details  
Pre-assignment Details  
Arm/Group Title GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Hide Arm/Group Description

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Period Title: Overall Study
Started 30 13
Completed 0 0
Not Completed 30 13
Reason Not Completed
Never rec'd study drug             0             1
Adverse Event             1             1
Withdrawal by Subject             1             0
Death             1             0
Progessive disease             27             11
Arm/Group Title GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma) Total
Hide Arm/Group Description

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Total of all reporting groups
Overall Number of Baseline Participants 30 12 42
Hide Baseline Analysis Population Description
One participant in the AG cohort was not evaluable/did not receive study drug.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 12 participants 42 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
29
  96.7%
12
 100.0%
41
  97.6%
>=65 years
1
   3.3%
0
   0.0%
1
   2.4%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 30 participants 12 participants 42 participants
46  (12) 42  (10) 44  (11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 12 participants 42 participants
Female
7
  23.3%
3
  25.0%
10
  23.8%
Male
23
  76.7%
9
  75.0%
32
  76.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 12 participants 42 participants
Hispanic or Latino
0
   0.0%
1
   8.3%
1
   2.4%
Not Hispanic or Latino
29
  96.7%
11
  91.7%
40
  95.2%
Unknown or Not Reported
1
   3.3%
0
   0.0%
1
   2.4%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 30 participants 12 participants 42 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   3.3%
0
   0.0%
1
   2.4%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
28
  93.3%
10
  83.3%
38
  90.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
1
   3.3%
2
  16.7%
3
   7.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 30 participants 12 participants 42 participants
30 12 42
1.Primary Outcome
Title Response, Defined as Stable Disease or Objective (Partial or Complete) Response.
Hide Description Complete response (CR) is complete disappearance of all measurable and evaluable disease. No new lesions. No evidence of non-evaluable disease. All measurable, evaluable and non-evaluable lesions and site must be assessed using the same techniques as baseline. Patients who respond must be on the same or decreasing doses of dexamethasone. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable disease. No new lesions. All measurable and evaluable lesions and sites must be assessed using same techniques as baseline. Responders must be on the same decreasing doses of dexamethasone. Stable disease (SD) does not qualify for CR, PR, or progression (e.g., a 25% increase in the sum of products of all measurable lesions). The designation of stable/no response requires a minimum of 6 weeks duration. All measurable and evaluable sites must be assessed using the same techniques as baseline.
Time Frame Patients were followed for an average of six weeks for assessment of response
Hide Outcome Measure Data
Hide Analysis Population Description
Two patients were not able to complete follow-up neuroimaging to assess response due to clinical progression of disease.
Arm/Group Title GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Hide Arm/Group Description:

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Overall Number of Participants Analyzed 28 12
Measure Type: Number
Unit of Measure: Participants
Complete response 0 0
Partial response 0 0
Stable disease 1 0
Progressive disease 27 12
2.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Time Frame 7.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Hide Arm/Group Description:

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Overall Number of Participants Analyzed 30 12
Measure Type: Number
Unit of Measure: Participants
30 12
3.Secondary Outcome
Title Adverse Event Grades
Hide Description The combined serious and non-serious adverse event Table describes count of patients whose highest grade adverse event for any CTC (common terminology criteria) term was related to study drugs for the GBM (Glioblastoma multiforme) and AG (Anaplastic glioma) cohorts.
Time Frame 7.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Neither cohort completed planned accrual and are small in number separately. Additionally, the underlying histological grade would not affect toxicity. Therefore, these cohorts may be combined. The Table describes count of patients whose highest grade adverse event for any CTC (common terminology criteria) term was related to study drugs.
Arm/Group Title Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Total
Hide Arm/Group Description:
Mild adverse event
Moderate adverse event
Severe adverse event
Life-threatening or disabling adverse event
Death related to adverse event
Total number of participants.
Overall Number of Participants Analyzed 42 42 42 42 42 42
Measure Type: Number
Unit of Measure: participants
thrombocytopenia 19 3 1 1 0 24
lymphopenia 4 4 4 0 0 12
hypophosphatemia 0 6 3 0 0 9
ALT/sGPT 6 1 0 0 0 7
anemia (Decreased Hgb) 6 0 0 0 0 6
hyponatremia 4 0 1 0 0 5
headache 0 2 1 0 0 3
leukopenia 1 2 0 0 0 3
AST/sGOT 2 0 0 0 0 2
dyspnea 1 0 1 0 0 2
fatigue 2 0 0 0 0 2
fever 1 1 0 0 0 2
hyperkalemia 2 0 0 0 0 2
cough 1 0 0 0 0 1
depression (mood alteration) 0 1 0 0 0 1
diarrhea 0 1 0 0 0 1
dizziness 1 0 0 0 0 1
venous thrombosis 0 0 1 0 0 1
edema 1 0 0 0 0 1
hyperbilirubinemia 1 0 0 0 0 1
hypermagnesemia 1 0 0 0 0 1
hypocalcemia 1 0 0 0 0 1
hypokalemia 1 0 0 0 0 1
hypotension 1 0 0 0 0 1
elevated creatinine 1 0 0 0 0 1
infection with unknown ANC 0 0 1 0 0 1
neutropenia 0 1 0 0 0 1
pain 0 1 0 0 0 1
rash 1 0 0 0 0 1
hemorrhage (rectal) 1 0 0 0 0 1
somnolence 0 0 1 0 0 1
urinary frequency 1 0 0 0 0 1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Hide Arm/Group Description

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

Bortezomib : intravenous (IV) injection 1.3 mg/m^2 days 3, 6, 10, 13, 24, 27,31,34 on every 6 week cycle

Tamoxifen citrate : oral dose 120 mg twice a day, every day

All-Cause Mortality
GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/30 (36.67%)      3/12 (25.00%)    
Blood and lymphatic system disorders     
Platelets  1  1/30 (3.33%)  2 0/12 (0.00%)  0
Gastrointestinal disorders     
Speech impairment (e.g., dysphagia or aphasia)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Diarrhea  1  0/30 (0.00%)  0 1/12 (8.33%)  1
General disorders     
Death not associated with CTCAE term: Death NOS  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Death not associated with CTCAE term: Disease progression NOS  1  4/30 (13.33%)  4 0/12 (0.00%)  0
Fatigue (asthenia, lethargy, malaise)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Fever (in the absence of neutropenia, where neutropenia is defined as ANC<1.0 x 10e9/L)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
Infection - Other (Specify, infection w/unknown ANC)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Infection  1 [1]  0/30 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders     
Muscle weakness, genralized or specific area (not due to neuropathy): Right-sided  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Nervous system disorders     
Neuropathy: motor  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Pain: head/headache  1  2/30 (6.67%)  2 0/12 (0.00%)  0
Seizure  1  4/30 (13.33%)  4 1/12 (8.33%)  2
Somnolence/depressed level of consciousness  1  1/30 (3.33%)  2 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea (shortness of breath)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Vascular disorders     
Vascular - Other (Specify-deep vein thrombosis)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCv3.0
[1]
Other, specify - shingles R T9 & T10 dermatomes both anteriorly & posteriorly, w/herpetic neuralgia pain.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
GBM (Glioblastoma Multiforme) AG (Anaplastic Glioma)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/30 (86.67%)      10/12 (83.33%)    
Blood and lymphatic system disorders     
Blood/Bone Marrow - Other (Specify, elevated white blood count;)  1 [1]  2/30 (6.67%)  2 0/12 (0.00%)  0
Edema: limb  1  2/30 (6.67%)  2 0/12 (0.00%)  0
Hemoglobin  1  4/30 (13.33%)  6 0/12 (0.00%)  0
Leukocytes (total WBC)  1  2/30 (6.67%)  3 2/12 (16.67%)  2
Lymphatics - Other (Specify)  1 [2]  1/30 (3.33%)  1 0/12 (0.00%)  0
Lymphopenia  1  10/30 (33.33%)  14 0/12 (0.00%)  0
Neutrophils/granulocytes (ANC/AGC)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Platelets  1  13/30 (43.33%)  21 4/12 (33.33%)  5
Cardiac disorders     
Hypotension  1  1/30 (3.33%)  2 1/12 (8.33%)  1
Eye disorders     
Nystagmus  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Ocular/Visual - Other (Specify, horizontal diplopia)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Vision-flashing lights/floaters  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Vision-blurred vision  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Gastrointestinal disorders     
Anorexia  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Constipation  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Nausea  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Hemorrhage: GI: Rectum  1  0/30 (0.00%)  0 1/12 (8.33%)  1
General disorders     
Death not associated with CTCAE term: Disease progression NOS  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Fatigue (asthenia, lethargy, malaise)  1  4/30 (13.33%)  4 1/12 (8.33%)  1
Fever (in the absence of neutropenia, where neutropenia is defined as ANC<1.0 x 10e9/L)  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Pain - Other (Specify, L side - hip and rib)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Weight gain  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Constitutional symptoms - Other (Specify, fatigue)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations     
Infection  1 [3]  0/30 (0.00%)  0 1/12 (8.33%)  1
Metabolism and nutrition disorders     
ALT, SGPT (serum glutamic pyruvic transaminase)  1  7/30 (23.33%)  7 3/12 (25.00%)  3
Albumin, serum-low (hypoalbuminemia)  1  4/30 (13.33%)  4 1/12 (8.33%)  1
Calcium, serum-low (hypocalcemia)  1  2/30 (6.67%)  2 1/12 (8.33%)  2
Magnesium, serum-high (hypermagnesemia)  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Phosphate, serum-low (hypophosphatemia)  1  6/30 (20.00%)  6 3/12 (25.00%)  4
Potassium, serum-high (hyperkalemia)  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Sodium, serum-low (hyponatremia)  1  4/30 (13.33%)  5 0/12 (0.00%)  0
Bicarbonate, serum-low  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Bilirubin (hyperbilirubinemia)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Calcium, serum-high (hypercalcemia)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Creatinine  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Glucose, serum-high (hyperglycemia)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
AST, SGOT (serum glutamic oxaloacetic transaminase)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Sodium, serum-high (hypernatremia)  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders     
Extremity - lower (gait-walking)  1  1/30 (3.33%)  2 0/12 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy): Facial  1  2/30 (6.67%)  2 0/12 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy): Left-sided  1  7/30 (23.33%)  7 0/12 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy): Right-sided  1  2/30 (6.67%)  2 0/12 (0.00%)  0
Muscle weakness, generalized or specific area (not due to neuropathy): Whole-body/generalized  1  1/30 (3.33%)  2 1/12 (8.33%)  1
Pain: Back  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Osteoporosis  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Nervous system disorders     
Ataxia  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Cognitive disturbance  1  2/30 (6.67%)  2 0/12 (0.00%)  0
Confusion  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Dizziness  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Memory impairment  1  1/30 (3.33%)  1 0/12 (0.00%)  0
Mood alteration: depression  1  2/30 (6.67%)  2 0/12 (0.00%)  0
Neuropathy: motor  1  3/30 (10.00%)  5 1/12 (8.33%)  1
Neuropathy: sensory  1  1/30 (3.33%)  2 0/12 (0.00%)  0
Pain: head/headache  1  3/30 (10.00%)  4 0/12 (0.00%)  0
Seizure  1  4/30 (13.33%)  5 1/12 (8.33%)  1
Somnolence/depressed level of consciousness  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Speech impairment (e.g., dysphagia or aphasia)  1  7/30 (23.33%)  7 1/12 (8.33%)  1
Renal and urinary disorders     
Urinary frequency/urgency  1  0/30 (0.00%)  0 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders     
Dyspnea (shortness of breath)  1  1/30 (3.33%)  1 1/12 (8.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCv3.0
[1]
Patient's platelets kept dropping and was 27 on 12/12, RBC-3.45, Hgb-10.6, Hct 30.8
[2]
displayed signs of bilateral edema in his feet/ankle area, lt pitting edema
[3]
(documented clinically or microbiologically) with Grade 3 or 4 neutrophils (ANC<1.0x10e9/L): lung (pneumonia)
Certain Agreements
Principal Investigators are NOT 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Kathy Warren, M.D.
Organization: National Cancer Institute
Phone: 301-435-4683
EMail: warrenk@box-w.nih.gov
Layout table for additonal information
Responsible Party: Katherine E. Warren, M.D., National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier: NCT00108069     History of Changes
Obsolete Identifiers: NCT00112762
Other Study ID Numbers: 050137
05-C-0137
First Submitted: April 12, 2005
First Posted: April 13, 2005
Results First Submitted: March 6, 2014
Results First Posted: June 12, 2014
Last Update Posted: November 5, 2015