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NCT Number: NCT02781792

Temozolomide Chronotherapy for High Grade Glioma

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.

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Key information

Conditions

Glioma Astrocytoma Glioblastoma Glioblastoma Multiforme Neoplasms Neoplasms by Histologic Type Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Newly diagnosed and recurrent high grade gliomas (WHO grades III & IV) and high risk WHO grade II gliomas who are to begin treatment with monthly high dose temozolomide therapy.
  • Scheduled to receive adjuvant temozolomide therapy after having completed concurrent temozolomide and radiation therapy.
  • At least 18 years of age.
  • Karnofsky performance status ≥ 60%
  • Ability to understand and willingness to sign an IRB approved written informed consent document

Exclusion criteria

.

-Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

Treatment and study plan

Temozolomide

Drug

-Given standard of care

Other names: Temodar

Functional Assessment of Cancer Therapy - Brain

Other
  • 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.

Other names: FACT-Br

ActTrust Condor Instrument Watch

Other

-Will be required to wear 24 hours per day and will only be removed at specified data collection time points

Primary outcomes

  1. Feasibility of Patient Treatment Compliance as Measured by Number of Participants Who Were at Least 80% Compliance With 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)

    Compliance is defined as no more than one of five doses of temozolomide per cycle taken outside of the assigned administration time.

  2. Duration of Response

    Time frame: Through completion of follow-up (estimated to be 30 months)

    • 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).

Secondary outcomes

  1. Number of Patients Experiencing Grade 3 or 4 Lymphopenia, Thrombocytopenia, Neutropenia, Leukopenia, and Anemia in Each Group as Measured by Standard Blood Draws

    Time frame: Through completion of treatment (median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles)

    • 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

  2. Change in Quality of Life as Measured by FACT-Br Score - Physical Well-being Score

    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))

    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.

  3. Change in Quality of Life as Measured by FACT-Br Score - Social/Family Well-being Score

    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))

    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.

  4. Change in Quality of Life as Measured by FACT-Br Score - Emotional Well-being Score

    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))

    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.

  5. Change in Quality of Life as Measured by FACT-Br Score - Functional Well-being Score

    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))

    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.

  6. Median Progression-free Survival (PFS)

    Time frame: Through completion of follow-up (median length of follow-up 568.5 days, full range 1-1134 days)

    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  7. Median Overall Survival

    Time frame: Through completion of follow-up (median length of follow-up 568.5 days, full range 1-1134 days)

  8. Comparison of Sleep Questionnaire in Participants Receiving Temozolomide in the Morning Versus Participants Receiving Temozolomide in the Evening

    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))

    Sleep Questionnaire - 1 yes/no question of "do you have problems getting to sleep or staying asleep?"

  9. Comparison of Sleep Questionnaire in Participants Receiving Temozolomide in the Morning Versus Participants Receiving Temozolomide in the Evening

    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))

    • 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.

  10. Mean Circadian Amplitude

    Time frame: From start of treatment through 2 months after end of treatment (median length 100 days, full range 78-240 days)

    • 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.

  11. Mean Sleep Regularity Index (SRI)

    Time frame: From start of treatment through 2 months after end of treatment (median length 100 days, full range 78-240 days)

    • 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.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Registry information

Official study title

A Randomized Feasibility Study Evaluating Temozolomide Chronotherapy for High Grade Glioma

Important dates

Study start
2016
Primary completion
2024
Study completion
2024
First posted
May 24, 2016
Registry last updated
Jun 27, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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