Temozolomide Chronotherapy for High Grade Glioma

Glioma Clinical Trial

Official title:

A Randomized Feasibility Study Evaluating Temozolomide Chronotherapy for High Grade Glioma

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02781792
• Other study ID #: 201605081
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 11, 2016
• Est. completion date: July 14, 2024

Study information

• Verified date: October 2023
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 42
• Est. completion date: July 14, 2024
• Est. primary completion date: July 14, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme
• Glioma

Intervention

Drug:
• Temozolomide
-Given standard of care

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.
• ActTrust Condor Instrument Watch
-Will be required to wear 24 hours per day and will only be removed at specified data collection time points

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility of patient treatment compliance as measured by 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.	Completion of treatment (estimated to be 6 months)
Primary	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).	Through completion of follow-up (estimated to be 30 months)
Secondary	Number of patients experiencing grade 3 or 4 lymphopenia, thrombocytopenia, neutropenia and anemia in each group as measured by standard blood draws	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	Completion of treatment (estimated to be 6 months)
Secondary	Quality of life as measured by FACT-Br score		1 month after completion of treatment (estimated to be 7 months)
Secondary	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.	Through completion of follow-up (estimated to be 30 months)
Secondary	Overall survival		Through completion of follow-up (estimated to be 30 months)
Secondary	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	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	Through 1 month after completion of treatment (estimated to be 7 months)

External Links

•   Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine