Brain Cancer
Conditions
Keywords
brain tumor, brain cancer, glioma
Brief summary
This pilot phase II trial studies how well giving temozolomide, bevacizumab, lithium carbonate, and radiation therapy works in treating patients with newly diagnosed high grade glioma.
Detailed description
Treatment of high grade glioma (HGG) with anti-angiogenic therapy results in clinical improvement and prolonged progression-free survival (PFS). However, mant patients experience diffuse recurrence and treatment failure. This is a phase II trial testing the feasibility of adding lithium carbonate, previously shown to have anti-invasive properties in HGG, to bevacizumab and chemoradiation following surgical resection of HGG.
Interventions
DRUGTemozolomide
DRUGBevacizumab
DRUGLithium Carbonate
RADIATIONRadiation
Sponsors
Genentech, Inc.
Atlantic Health System
NYU Langone Health
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed high grade glioma (WHO Grade III and IV) * Brain magnetic resonance imaging (MRI) scan with gadolinium contrast * Patient must have normal organ and marrow function as defined below: * Absolute neutrophil count \>= 1,500/mm\^3; * Platelet count \>=100,000/mm\^3; * Hemoglobin \>= 10g/dL; * Blood urea nitrogen and serum creatinine both =\< 1.5 times upper limit of normal (ULN); * Total bilirubin both =\< 1.5 times ULN; * SGOT and SGPT both =\< 3 times ULN; * Alkaline phosphatase =\< 2 times ULN. * \>=18 years of age; * Karnofsky Performance Score \>= 70; * Life expectancy \>= 8 weeks; * Negative serum or urine beta-hCG pregnancy test at screening for patients of child bearing potential; * Men and women with reproductive potential must agree to use an acceptable method of birth control (surgical, hormonal or double barrier, ie, condom and diaphragm) during treatment and for 6 months after completion of treatment; * Patient or their legal proxy must provide written informed consent prior to registration on study; * Residual measurable disease.
Exclusion criteria
* Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study; * Prior radiation therapy to the brain; * Prior treatment with Chemotherapy or Targeted agent * Previous (within last 5 years) or current malignancies at other sites except for adequately treated basal cell or squamous cell skin cancer in situ carcinoma of the cervix; * (Uncontrolled High blood pressure \>150/100 * Common Terminology Criteria Adverse Event 3.0 \>= Grade 2 congestive heart failure (CHF); * History of myocardial infarction within 6 months; * History of stroke within 6 months; * Clinically significant peripheral vascular disease; * Evidence of bleeding diathesis or coagulopathy; * Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of bevacizumab or anticipation of need for major surgical procedure during the course of the study; * Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to study enrollment; * Urine protein/Creatinine ratio \>= 2.0 at screening; * Serious, non-healing wound, ulcer, or bone fracture; * Inability to comply with study and/or follow-up procedures; * Glioma showing active intratumoral bleeding; * Patients on enzyme-inducing anti-epileptic drugs; * Known Positive HIV-1, hepatitis B surface antigen, or hepatitis C antibody; * Medications like nonsteroidal antiinflammatory drugs, antipsychotics, iodides, and angiotensin-converting enzyme inhibitor, If they are receiving them, they must have been discontinued for 7 days prior to initiating lithium; * Any previous cytotoxic drug therapies, excluding corticosteroids and temozolomide concurrent with radiation therapy; * Any known genetic cancer-susceptibility syndromes; * Acute infection: any active viral, bacterial, or fungal infection that requires specific therapy. * Active uncontrolled infection - examples include sexually transmitted disease, herpes, scrofula, malaria, etc.; * Fever \> 101.5 degrees Fahrenheit; * Unstable or severe intercurrent medical conditions such as unstable angina, uncontrolled arrythmias, Crohn's disease, ulcerative colitis, psoriasis, etc.; * Implantation of Gliadel wafers at surgery; * Patients with organ allografts; and * Allergies to reagents used in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Progression-Free Survival (PFS) | Up to 50 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival (OS) | Up to 50 months | OS defined as time from diagnosis to most recent follow up or death. |
| Number of Patients With Grade 3 or 4 Adverse Events | The whole time while on treatment and 30 days after the treatment | Adverse events evaluated per CTCAE 3 |
Countries
United States
Participant flow
Recruitment details
From June 2010 to June 2012, 28 patients were enrolled from New York University Langone Medical Center and Outlook Hospital, Summit, NJ.
Participants by arm
| Arm | Count |
|---|---|
| TBL/RT 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. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | TBL/RT |
|---|---|
| Age, Continuous | 56 years |
| Race/Ethnicity, Customized Asian | 1 participants |
| Race/Ethnicity, Customized Caucasian | 26 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 16 Participants |
| World Health Organization Grade (staging) Grade III | 8 participants |
| World Health Organization Grade (staging) Grade IV | 20 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 26 / 28 |
| serious Total, serious adverse events | 7 / 28 |
Outcome results
Primary
Median Progression-Free Survival (PFS)
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
Population: Intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TBL/RT | Median Progression-Free Survival (PFS) | 9.4 months |
Secondary
Median Overall Survival (OS)
OS defined as time from diagnosis to most recent follow up or death.
Time frame: Up to 50 months
Population: intent-to-treat population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| TBL/RT | Median Overall Survival (OS) | 18.5 months |
Secondary
Number of Patients With Grade 3 or 4 Adverse Events
Adverse events evaluated per CTCAE 3
Time frame: The whole time while on treatment and 30 days after the treatment
Population: all the patients with treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Dermatitis | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | DVT | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Neurologic | 3 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Pneumonia | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Rash | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Cough | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Hyponatremia | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Gastrointestinal | 2 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Febril Neutropenia | 0 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Neutropenia | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Thrombocytopenia | 1 participants |
| TBL/RT | Number of Patients With Grade 3 or 4 Adverse Events | Somnolence | 1 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Cough | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Dermatitis | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Febril Neutropenia | 1 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | DVT | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Somnolence | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Hyponatremia | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Neurologic | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Thrombocytopenia | 1 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Pneumonia | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Gastrointestinal | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Rash | 0 participants |
| Grade 4 | Number of Patients With Grade 3 or 4 Adverse Events | Neutropenia | 0 participants |