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Temodar (Temozolomide), Bevacizumab, Lithium and Radiation for High Grade Glioma

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ClinicalTrials.gov Identifier: NCT01105702
Recruitment Status : Terminated (Due to slow accrual)
First Posted : April 16, 2010
Results First Posted : November 6, 2015
Last Update Posted : August 4, 2016
Sponsor:
Collaborators:
Genentech, Inc.
Atlantic Health System
Information provided by (Responsible Party):
NYU Langone Health

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain Cancer
Interventions Drug: Temozolomide
Drug: Bevacizumab
Drug: Lithium Carbonate
Radiation: Radiation
Enrollment 28
Recruitment Details From June 2010 to June 2012, 28 patients were enrolled from New York University Langone Medical Center and Outlook Hospital, Summit, NJ.
Pre-assignment Details  
Arm/Group Title TBL/RT
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Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
Period Title: Overall Study
Started 28
Completed 10
Not Completed 18
Arm/Group Title TBL/RT
Hide Arm/Group Description

Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
All patients enrolled
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 28 participants
56
(23 to 77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female
12
  42.9%
Male
16
  57.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants
Caucasian 26
Asian 1
Hispanic 1
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 28 participants
28
World Health Organization Grade (staging)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 28 participants
Grade III 8
Grade IV 20
[1]
Measure Description:

Grade III: Malignant although there is not always a big difference between grade II and grade III tumors. The cells of a grade III tumor are actively reproducing abnormal cells, which grow into nearby normal brain tissue. These tumors tend to recur, often as a grade IV.

Grade IV: These are the most malignant tumors. They reproduce rapidly, can have a bizarre appearance when viewed under the microscope, and easily grow into nearby normal brain tissue. These tumors form new blood vessels so they can maintain their rapid growth.

1.Primary Outcome
Title Median Progression-Free Survival (PFS)
Hide Description PFS defined as time from date of diagnosis to most recent follow up, disease progression, or death. Disease progress defined as either clinical deterioration or radiographic progressive disease on magnetic resonance imaging (MRI) per updated response assessment in neuro-oncology criteria (Wen, et al).
Time Frame Up to 50 months
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Hide Analysis Population Description
Intent-to-treat population
Arm/Group Title TBL/RT
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Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: months
9.4
(6.1 to 12.4)
2.Secondary Outcome
Title Median Overall Survival (OS)
Hide Description OS defined as time from diagnosis to most recent follow up or death.
Time Frame Up to 50 months
Hide Outcome Measure Data
Hide Analysis Population Description
intent-to-treat population
Arm/Group Title TBL/RT
Hide Arm/Group Description:

Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
Overall Number of Participants Analyzed 28
Median (95% Confidence Interval)
Unit of Measure: months
18.5
(14.7 to 20.8)
3.Secondary Outcome
Title Number of Patients With Grade 3 or 4 Adverse Events
Hide Description Adverse events evaluated per CTCAE 3
Time Frame The whole time while on treatment and 30 days after the treatment
Hide Outcome Measure Data
Hide Analysis Population Description
all the patients with treatment
Arm/Group Title Grade 3 Grade 4
Hide Arm/Group Description:

Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.

Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
Overall Number of Participants Analyzed 28 28
Measure Type: Number
Unit of Measure: participants
Dermatitis 1 0
DVT 1 0
Neurologic 3 0
Pneumonia 1 0
Rash 1 0
Cough 1 0
Hyponatremia 1 0
Gastrointestinal 2 0
Febril Neutropenia 0 1
Neutropenia 1 0
Thrombocytopenia 1 1
Somnolence 1 0
Time Frame whole time while on treatment plus 30 days after the treatment
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TBL/RT
Hide Arm/Group Description

Cycle 1(One 42-day cycle)

  • Temozolomide 75 mg/m^2 orally (42 consecutive days), beginning the night prior to the first radiation treatment
  • Radiation within 3-5 weeks of surgery
  • Bevacizumab 10mg/kg, IV, starting 29 (+3) days post surgery and every 2 weeks

Treatment Cycles 2-7 (28 days per cycle)

  • Temozolomide at a dose of 150 mg/m^2 on Days 1-7
  • Bevacizumab 10 mg/kg on Day 8 and Day 22
  • Initiate Lithium carbonate treatment at 300 mg, orally, twice a day; dose increased every 7 days up to 600mg, orally, twice a day, to a serum lithium level of 0.8-1.2 mEq/L.
All-Cause Mortality
TBL/RT
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
TBL/RT
Affected / at Risk (%)
Total   7/28 (25.00%) 
Blood and lymphatic system disorders   
Febrile neutropenia  1  1/28 (3.57%) 
Ear and labyrinth disorders   
Tinnitus  1  1/28 (3.57%) 
Gastrointestinal disorders   
Vomiting  1  1/28 (3.57%) 
Infections and infestations   
Infection with unknown ANC: Wound  1  1/28 (3.57%) 
Infection with unknown ANC: Lung (pneumonia)  1  1/28 (3.57%) 
Infection with unknown ANC: Eye NOS  1  1/28 (3.57%) 
Musculoskeletal and connective tissue disorders   
Pain - Other (Specify, __): jaw  1  1/28 (3.57%) 
Nervous system disorders   
Neuropathy: sensory  1  1/28 (3.57%) 
Seizure  1  2/28 (7.14%) 
Dizziness  1  1/28 (3.57%) 
Vascular disorders   
Thrombosis/thrombus/embolism  1  2/28 (7.14%) 
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 0%
TBL/RT
Affected / at Risk (%)
Total   26/28 (92.86%) 
Blood and lymphatic system disorders   
Edema: limb  1  1/28 (3.57%) 
Neutrophils/granulocytes (ANC/AGC)  1  1/28 (3.57%) 
Platelets  1  3/28 (10.71%) 
Cardiac disorders   
Hypertension  1  1/28 (3.57%) 
Supraventricular and nodal arrhythmia: Sinus bradycardia  1  1/28 (3.57%) 
Ear and labyrinth disorders   
Auditory/Ear - Other (Specify, __): flud in right ear  1  1/28 (3.57%) 
Hearing: patients without baseline audiogram and not enrolled in a monitoring program  1  1/28 (3.57%) 
Pain: Middle ear  1  1/28 (3.57%) 
Endocrine disorders   
Thyroid function, high (hyperthyroidism, thyrotoxicosis)  1  2/28 (7.14%) 
Eye disorders   
Nystagmus  1  1/28 (3.57%) 
Vision-blurred vision  1  5/28 (17.86%) 
Vision-flashing lights/floaters  1  1/28 (3.57%) 
Gastrointestinal disorders   
Anorexia  1  9/28 (32.14%) 
Constipation  1  9/28 (32.14%) 
Dental: periodontal disease  1  1/28 (3.57%) 
Diarrhea  1  3/28 (10.71%) 
Heartburn/dyspepsia  1  2/28 (7.14%) 
Hemorrhage, GI: Oral cavity  1  3/28 (10.71%) 
Hemorrhage, GI: Rectum  1  1/28 (3.57%) 
Mucositis/stomatitis (clinical exam): Stomach  1  1/28 (3.57%) 
Nausea  1  8/28 (28.57%) 
Pain: Dental/teeth/peridontal  1  1/28 (3.57%) 
Pain: Stomach  1  1/28 (3.57%) 
Taste alteration (dysgeusia)  1  3/28 (10.71%) 
Vomiting  1  2/28 (7.14%) 
General disorders   
Fatigue (asthenia, lethargy, malaise)  1  16/28 (57.14%) 
Insomnia  1  4/28 (14.29%) 
Pain: Chest/thorax NOS  1  1/28 (3.57%) 
Sweating (diaphoresis)  1  1/28 (3.57%) 
Weight loss:  1  1/28 (3.57%) 
Infections and infestations   
Infection - Other (Specify, __): thrush  1  1/28 (3.57%) 
Infection - Other (Specify, __): Urinary tract infection  1  1/28 (3.57%) 
Infection with normal ANC or Grade 1 or 2 neutrophils: Urinary tract NOS  1  1/28 (3.57%) 
Metabolism and nutrition disorders   
Calcium, serum-high (hypercalcemia)  1  1/28 (3.57%) 
Cholesterol, serum-high (hypercholestremia)  1  1/28 (3.57%) 
Sodium, serum-low (hyponatremia)  1  1/28 (3.57%) 
Musculoskeletal and connective tissue disorders   
Muscle weakness, generalized or specific area (not due to neuropathy): Extremity-lower  1  2/28 (7.14%) 
Muscle weakness, generalized or specific area (not due to neuropathy): Whole body/generalized  1  3/28 (10.71%) 
Pain: Back  1  1/28 (3.57%) 
Pain: Bone  1  1/28 (3.57%) 
Pain: Extremity-limb  1  3/28 (10.71%) 
Nervous system disorders   
Ataxia (incoordination)  1  1/28 (3.57%) 
Confusion  1  1/28 (3.57%) 
Dizziness  1  1/28 (3.57%) 
Memory impairment  1  2/28 (7.14%) 
Mood alteration: Anxiety  1  3/28 (10.71%) 
Mood alteration: Depression  1  2/28 (7.14%) 
Neuropathy: cranial- Pupil, upper eyelid, extra ocular movements  1  1/28 (3.57%) 
Neuropathy: cranial- sensory facial  1  1/28 (3.57%) 
Neuropathy: Cranial-smell  1  1/28 (3.57%) 
Neuropathy: sensory  1  4/28 (14.29%) 
Pain: Head/headache  1  11/28 (39.29%) 
Seizure  1  2/28 (7.14%) 
Somnolence/depressed level of consciousness  1  1/28 (3.57%) 
Speech impairment (e.g., dysphasia or aphasia)  1  3/28 (10.71%) 
Syncope (fainting)  1  1/28 (3.57%) 
Tremor  1  2/28 (7.14%) 
Psychiatric disorders   
Psychosis (hallucinations/delusions)  1  1/28 (3.57%) 
Renal and urinary disorders   
Urinary frequency/urgency  1  1/28 (3.57%) 
Urinary retention (including neurogenic bladder)  1  1/28 (3.57%) 
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip):  1  1/28 (3.57%) 
Cough  1  3/28 (10.71%) 
Dyspnea (shortness of breath)  1  1/28 (3.57%) 
Hemorrhage, pulmonary/upper respiratory: Nose  1  1/28 (3.57%) 
Nasal cavity/paranasal sinus reactions  1  1/28 (3.57%) 
Voice changes/dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)  1  1/28 (3.57%) 
Skin and subcutaneous tissue disorders   
Dry skin  1  1/28 (3.57%) 
Flushing  1  1/28 (3.57%) 
Hair loss/alopecia (scalp or body)  1  4/28 (14.29%) 
Pruritus/itching  1  1/28 (3.57%) 
Rash/desquamation  1  2/28 (7.14%) 
Rash: acne/acneiform  1  2/28 (7.14%) 
Rash: dermatitis associated with radiation: Chemoradiation  1  1/28 (3.57%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Michael Gruber, MD
Organization: Perlmutter Cancer Center at NYU Langone
Phone: 212-731-5577
EMail: michael.gruber@nyumc.org
Layout table for additonal information
Responsible Party: NYU Langone Health
ClinicalTrials.gov Identifier: NCT01105702    
Other Study ID Numbers: NYU 07-712
First Submitted: April 12, 2010
First Posted: April 16, 2010
Results First Submitted: October 5, 2015
Results First Posted: November 6, 2015
Last Update Posted: August 4, 2016