Temozolomide Chronotherapy for High Grade Glioma

The Washington University

Status and phase: Completed; Phase 2

Conditions: Glioma; Glioblastoma Multiforme

Treatments: Drug: Temozolomide; Other: Functional Assessment of Cancer Therapy - Brain; Other: ActTrust Condor Instrument Watch

Study type: Interventional

Funder types: Other

Identifiers

NCT02781792

201605081

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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42 participants in 2 patient groups

Arm 1: Temozolomide morning

Experimental group

Description:

* 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

Treatment:

Other: ActTrust Condor Instrument Watch

Other: Functional Assessment of Cancer Therapy - Brain

Drug: Temozolomide

Arm 2: Temozolomide evening

Experimental group

Description:

* 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

Treatment:

Other: ActTrust Condor Instrument Watch

Other: Functional Assessment of Cancer Therapy - Brain

Drug: Temozolomide