Phase 2
Completed N=42
Temozolomide Chronotherapy for High Grade Glioma
Source: ClinicalTrials.gov NCT02781792 ↗Enrolled (actual)
42
Serious AEs
26.2%
Results posted
Jun 2025
Primary outcomePrimary: Feasibility of Patient Treatment Compliance as Measured by Number of Participants Who Were at Least 80% Compliance With Assigned Administration Time — 17; 15 Participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Feasibility of Patient Treatment Compliance as Measured by Number of Participants Who Were at Least 80% Compliance With Assigned Administration Time |
17; 15 | — |
| PRIMARY Duration of Response |
— | — |
| SECONDARY Number of Patients Experiencing Grade 3 or 4 Lymphopenia, Thrombocytopenia, Neutropenia, Leukopenia, and Anemia in Each Group as Measured by Standard Blood Draws |
2; 0; 1; 0; 0; 1 | — |
| SECONDARY Change in Quality of Life as Measured by FACT-Br Score - Physical Well-being Score |
6.23; 4.80; 5.78; 4.00; 7.66; 8.32 | — |
| SECONDARY Change in Quality of Life as Measured by FACT-Br Score - Social/Family Well-being Score |
24.10; 22.94; 24.29; 22.59; 22.45; 23.12 | — |
| SECONDARY Change in Quality of Life as Measured by FACT-Br Score - Emotional Well-being Score |
6.72; 7.60; 6.69; 8.11; 6.06; 6.77 | — |
| SECONDARY Change in Quality of Life as Measured by FACT-Br Score - Functional Well-being Score |
18.19; 16.35; 18.71; 15.89; 15.94; 16.11 | — |
| SECONDARY Median Progression-free Survival (PFS) |
11.5978; 8.1809 | — |
| SECONDARY Median Overall Survival |
26.9739; 17.1831 | — |
| SECONDARY Comparison of Sleep Questionnaire in Participants Receiving Temozolomide in the Morning Versus Participants Receiving Temozolomide in the Evening |
3; 1; 2; 1; 3; 2 | — |
| SECONDARY Comparison of Sleep Questionnaire in Participants Receiving Temozolomide in the Morning Versus Participants Receiving Temozolomide in the Evening |
3; 1; 2; 1; 3; 2 | — |
| SECONDARY Mean Circadian Amplitude |
0.78; 0.78; 0.81; 0.78; 0.77; 0.81 | — |
| SECONDARY Mean Sleep Regularity Index (SRI) |
0.70; 0.79; 0.82; 0.69; 0.68; 0.82 | — |
Eligibility Criteria
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.
Data sourced from ClinicalTrials.gov (NCT02781792). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.