Temozolomide (TMZ) is the chemotherapy drug approved by the FDA to increase survival in glioblastoma (GBM) patients beyond surgical resection and radiation therapy alone. Give its activity in astrocytomas, TMZ is commonly used in grade III anaplastic astrocytoma (AA) as well. Both grade III AA and grade IV GBM are high grade gliomas (HGG). The short half-life of this drug and known oscillations in DNA damage repair make it an ideal candidate for chronotherapy. Chronotherapy is the improvement of treatment outcomes by minimizing treatment toxicity and maximizing efficacy through delivery of a medication according to the timing of biological rhythms within a patient. Chronotherapy has improved outcomes through the reduction of side effects and increase in anti-tumor activity for a variety of cancers, but has never been applied to the treatment of gliomas. Based on the preliminary preclinical data for chronotherapeutic TMZ treatment of intracranial glioma xenografts and the success of chronotherapy in the treatment of other cancers, the investigators hypothesize that the timing of TMZ treatment will alter its efficacy and toxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
-Given standard of care
* 23-item questionnaire that can be completed in 5 to 10 minutes with little or no assistance in patients who are not neurologically incapacitated. This brain subscale is usually used along with the core (general) questionnaire \[2\] that includes 27 items. * Patients rate all 5 items using a five-point Likert scale ranging from 0 "not at all" to 4 "very much." Overall, higher ratings suggest higher QOL. Items are totaled to produce the following subscales, along with an overall QOL score: physical well-being (7 items); social/family well-being (7 items); emotional well-being (6 items); functional well-being (7 items); and concerns relevant to patients with brain tumors (23 items) * The sleep portion of this questionnaire consists of 17 questions about sleeping patterns and the ability to rate severity of insomnia.
-Will be required to wear 24 hours per day and will only be removed at specified data collection time points
Washington University School of Medicine
St Louis, Missouri, United States
Feasibility of Patient Treatment Compliance as Measured by Number of Participants Who Were at Least 80% Compliance With Assigned Administration Time
Compliance is defined as no more than one of five doses of temozolomide per cycle taken outside of the assigned administration time.
Time frame: Through completion of treatment (median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles)
Duration of Response
* Response and progression will be evaluated in this study using the updated response assessment criteria for high-grade gliomas: Response Assessment in Neuro-Oncology (RANO) working group guideline \[JCO 28(11): 1963-1972, 2010\]. * The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR) (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Time frame: Through completion of follow-up (estimated to be 30 months)
Number of Patients Experiencing Grade 3 or 4 Lymphopenia, Thrombocytopenia, Neutropenia, Leukopenia, and Anemia in Each Group as Measured by Standard Blood Draws
* Lymphopenia grade 3 is \<500-200/mm\^3 and grade 4 is \<200/mm\^3 * Leukopenia grade 3 is \<2000-1000/mm\^3 and grade 4 is \<1000/mm\^3 * Neutropenia grade 3 is \<1000-500/mm\^3 and grade 4 is \<500/mm\^3 * Thrombocytopenia grade 3 is \<50,000-25,000/mm\^3 and grade 4 is \<25,000/mm\^3 * Anemia grade 3 is \<8.0-6.5 g/dL and grade 4 is \<6.5 g/dL
Time frame: Through completion of treatment (median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles)
Change in Quality of Life as Measured by FACT-Br Score - Physical Well-being Score
7-item questionnaire measuring over the past 7 days. Answers range from 0=not at all to 4=very much. Total score range is 0-28. A higher score indicates a lower physical well-being quality of life.
Time frame: Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))
Change in Quality of Life as Measured by FACT-Br Score - Social/Family Well-being Score
7-item questionnaire measuring over the past 7 days. Answers range from 0=not at all to 4=very much. Total score range 0-28. A higher score indicates a higher social/family well-being quality of life.
Time frame: Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))
Change in Quality of Life as Measured by FACT-Br Score - Emotional Well-being Score
6-item questionnaire measuring over the past 7 days. Answers range from 0=not at all to 4=very much. Total score range 0-24. A higher score indicates a lower emotional well-being quality of life.
Time frame: Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))
Change in Quality of Life as Measured by FACT-Br Score - Functional Well-being Score
7-item questionnaire measuring over the past 7 days. Answers range from 0=not at all to 4=very much. Total score range 0-28. A higher score indicates a higher emotional well-being quality of life.
Time frame: Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))
Median Progression-free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time frame: Through completion of follow-up (median length of follow-up 568.5 days, full range 1-1134 days)
Median Overall Survival
Time frame: Through completion of follow-up (median length of follow-up 568.5 days, full range 1-1134 days)
Comparison of Sleep Questionnaire in Participants Receiving Temozolomide in the Morning Versus Participants Receiving Temozolomide in the Evening
Sleep Questionnaire - 1 yes/no question of "do you have problems getting to sleep or staying asleep?"
Time frame: Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))
Comparison of Sleep Questionnaire in Participants Receiving Temozolomide in the Morning Versus Participants Receiving Temozolomide in the Evening
\- Sleep Questionnaire: * Difficulty falling asleep/difficulty staying asleep/problem waking up too early: Answers range from 0=none, mild=1, moderate=2, severe=3, very=4. * How satisfied or dissatisfied are you with your current sleeping pattern question: Answers range from 0=very satisfied to 4=very dissatisfied. * To what extent do you consider your sleep problem to interfere with your daily functioning question: Answers range from 0=not at all interfering, 1=a little, 2=somewhat, 3=much, 4=very much interfering. * How noticeable to others do you think your sleep problem is in terms of impairing the quality of your life question: Answers range from 0=not at all noticeable, 1=barely, 2 = somewhat, 3 =much, 4=very noticeable. * How worried or distressed are you about your current sleep problem question: Answers range from 0=not at all=0, 1=a little, 2=somewhat, 3=much, 4=very much.
Time frame: Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))
Mean Circadian Amplitude
* The ActTrust Condor Instrument watches are wrist actimetry/accelerometers. Patients will wear an accelerometer on their wrist to measure activity level during the day and at night until two months after the end of treatment. * Circadian amplitude, refers to the difference between the highest and lowest points of a circadian rhythm over a 24-hour cycle, is typically measured in the units of the rhythm being quantified. * The circadian mean amplitude was calculated per day for each patient with the mean and standard deviation reported across all days for each individual patient.
Time frame: From start of treatment through 2 months after end of treatment (median length 100 days, full range 78-240 days)
Mean Sleep Regularity Index (SRI)
* The ActTrust Condor Instrument watches are wrist actimetry/accelerometers. Patients will wear an accelerometer on their wrist to measure activity level during the day and at night until two months after the end of treatment. * Sleep regularity index (SRI) is the probability of being at rest, calculated per day for each patient. An SRI closer to 0 indicates irregular sleep patterns (i.e., more variable day to day), while values closer to 1 indicate regular sleep patterns. The SRI index scale is 0\~1. * The SRI was calculated per day for each patient with the mean and standard deviation reported across all days for each individual patient.
Time frame: From start of treatment through 2 months after end of treatment (median length 100 days, full range 78-240 days)
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