Clinical trial NCT02781792: Temozolomide Chronotherapy for High Grade Glioma
Official title: A Randomized Feasibility Study Evaluating Temozolomide Chronotherapy for High Grade Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioma
Glioblastoma Multiforme
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-05-24
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Feasibility of patient treatment compliance as measured by at least 80% compliance with assigned administration time
timeFrame: Completion of treatment (estimated to be 6 months)
measure: Duration of response
timeFrame: Through completion of follow-up (estimated to be 30 months)
Secondary outcomes:
measure: Number of patients experiencing grade 3 or 4 lymphopenia, thrombocytopenia, neutropenia and anemia in each group as measured by standard blood draws
timeFrame: Completion of treatment (estimated to be 6 months)
measure: Quality of life as measured by FACT-Br score
timeFrame: 1 month after completion of treatment (estimated to be 7 months)
measure: Progression-free survival (PFS)
timeFrame: Through completion of follow-up (estimated to be 30 months)
measure: Overall survival
timeFrame: Through completion of follow-up (estimated to be 30 months)
measure: 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
timeFrame: Through 1 month after completion of treatment (estimated to be 7 months)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Milan Chheda, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Damato AR, Katumba RGN, Luo J, Atluri H, Talcott GR, Govindan A, Slat EA, Weilbaecher KN, Tao Y, Huang J, Butt OH, Ansstas G, Johanns TM, Chheda MG, Herzog ED, Rubin JB, Campian JL. A randomized feasibility study evaluating temozolomide circadian medicine in patients with glioma. Neurooncol Pract. 2022 Jan 31;9(3):193-200. doi: 10.1093/nop/npac003. eCollection 2022 May.