Temozolomide Chronotherapy for High Grade Glioma
- Conditions
- GliomaGlioblastoma Multiforme
- Interventions
- Other: Functional Assessment of Cancer Therapy - BrainOther: ActTrust Condor Instrument Watch
- Registration Number
- NCT02781792
- Lead Sponsor
- Washington University School of Medicine
- Brief 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 invesitgators hypothesize that the timing of TMZ treatment will alter its efficacy and toxicity.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- 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
.
-Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Temozolomide morning ActTrust Condor Instrument Watch * Temozolomide will be given as per standard of care. Typical dosing is 150 to 200 mg/m\^2 on Days 1 through 5 of a 28-day treatment cycle. Patients will be randomized to take their temozolomide doses in the morning (before 10:00). * FACT-Br quality of life at baseline, at the beginning of each cycle of chemotherapy, and 1 month after the final chemotherapy treatment Arm 2: Temozolomide evening Functional Assessment of Cancer Therapy - Brain * Temozolomide will be given as per standard of care. Typical dosing is 150 to 200 mg/m2 on Days 1 through 5 of a 28-day treatment cycle. Patients will be randomized to take their temozolomide doses in the evening (after 20:00). * FACT-Br quality of life at baseline, at the beginning of each cycle of chemotherapy, and 1 month after the final chemotherapy treatment Arm 2: Temozolomide evening ActTrust Condor Instrument Watch * Temozolomide will be given as per standard of care. Typical dosing is 150 to 200 mg/m2 on Days 1 through 5 of a 28-day treatment cycle. Patients will be randomized to take their temozolomide doses in the evening (after 20:00). * FACT-Br quality of life at baseline, at the beginning of each cycle of chemotherapy, and 1 month after the final chemotherapy treatment Arm 1: Temozolomide morning Temozolomide * Temozolomide will be given as per standard of care. Typical dosing is 150 to 200 mg/m\^2 on Days 1 through 5 of a 28-day treatment cycle. Patients will be randomized to take their temozolomide doses in the morning (before 10:00). * FACT-Br quality of life at baseline, at the beginning of each cycle of chemotherapy, and 1 month after the final chemotherapy treatment Arm 1: Temozolomide morning Functional Assessment of Cancer Therapy - Brain * Temozolomide will be given as per standard of care. Typical dosing is 150 to 200 mg/m\^2 on Days 1 through 5 of a 28-day treatment cycle. Patients will be randomized to take their temozolomide doses in the morning (before 10:00). * FACT-Br quality of life at baseline, at the beginning of each cycle of chemotherapy, and 1 month after the final chemotherapy treatment Arm 2: Temozolomide evening Temozolomide * Temozolomide will be given as per standard of care. Typical dosing is 150 to 200 mg/m2 on Days 1 through 5 of a 28-day treatment cycle. Patients will be randomized to take their temozolomide doses in the evening (after 20:00). * FACT-Br quality of life at baseline, at the beginning of each cycle of chemotherapy, and 1 month after the final chemotherapy treatment
- Primary Outcome Measures
Name Time Method Duration of response 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).Feasibility of patient treatment compliance as measured by at least 80% compliance with assigned administration time Completion of treatment (estimated to be 6 months) Compliance is defined as no more than one of five doses of temozolomide per cycle taken outside of the assigned administration time.
- Secondary Outcome Measures
Name Time Method Quality of life as measured by FACT-Br score 1 month after completion of treatment (estimated to be 7 months) Number of patients experiencing grade 3 or 4 lymphopenia, thrombocytopenia, neutropenia and anemia in each group as measured by standard blood draws Completion of treatment (estimated to be 6 months) * Lymphopenia grade 3 is \<500-200/mm3 and grade 4 is \<200/mm3
* Leukopenia grade 3 is \<2000-1000/mm3 and grade 4 is \<1000/mm3
* Neutropenia grade 3 is \<1000-500/mm3 and grade 4 is \<500/mm3
* Thrombocytopenia grade 3 is \<50,000-25,000/mm3 and grade 4 is \<25,000/mm3
* Anemia grade 3 is \<8.0-6.5 g/dL and grade 4 is \<6.5 g/dLProgression-free survival (PFS) Through completion of follow-up (estimated to be 30 months) PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Overall survival Through completion of follow-up (estimated to be 30 months) Comparison of the level of sleep disruption in sleep-wake cycles of participants receiving temozolomide in the morning versus participants receiving temozolomide in the evening Through 1 month after completion of treatment (estimated to be 7 months) * The data will be collected through the ActTrust Condor Instrument Watch and the Sleep Questionniare.
* The qualitative data (sleep questionnaire) will be used with quantitative data (collected via the ActTrust watch) to assess the level of sleep disruption in sleep/wake cycles
Trial Locations
- Locations (1)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States