Temozolomide Chronotherapy for High Grade Glioma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1: Temozolomide morning 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 |
Drug: Temozolomide
-Given standard of care
Other Names:
Other: Functional Assessment of Cancer Therapy - Brain
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:
Other: ActTrust Condor Instrument Watch
-Will be required to wear 24 hours per day and will only be removed at specified data collection time points
|
| Experimental: Arm 2: Temozolomide evening 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 |
Drug: Temozolomide
-Given standard of care
Other Names:
Other: Functional Assessment of Cancer Therapy - Brain
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:
Other: ActTrust Condor Instrument Watch
-Will be required to wear 24 hours per day and will only be removed at specified data collection time points
|
Outcome Measures
Primary Outcome Measures
- 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.
- Duration of response [Until disease progression (estimated to be 6 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 Outcome Measures
- 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/dL
- Quality of life as measured by FACT-Br score [1 month after completion of treatment (estimated to be 7 months)]
- Progression-free survival (PFS) [Until disease progression (estimated to be 6 months)]
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
- Overall survival [Until patient death (estimated to be 15 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
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
Sponsors and Collaborators
- Washington University School of Medicine
Investigators
- Principal Investigator: Milan Chheda, M.D., Washington University School of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 201605081