Temozolomide Chronotherapy for High Grade Glioma

NCT02781792 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 201605081
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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 investigators hypothesize that the timing of TMZ treatment will alter its efficacy and toxicity.

Conditions

Glioma; Glioblastoma Multiforme

Outcome Measures

Primary Outcomes (2)

• Feasibility of Patient Treatment Compliance as Measured by Number of Participants Who Were 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.

  Through completion of treatment (median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles)

• 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 Outcomes (11)

• Number of Patients Experiencing Grade 3 or 4 Lymphopenia, Thrombocytopenia, Neutropenia, Leukopenia, and Anemia in Each Group as Measured by Standard Blood Draws

  Through completion of treatment (median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles)

• Change in Quality of Life as Measured by FACT-Br Score - Physical Well-being Score

  Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))

• Change in Quality of Life as Measured by FACT-Br Score - Social/Family Well-being Score

  Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))

• Change in Quality of Life as Measured by FACT-Br Score - Emotional Well-being Score

  Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))

• Change in Quality of Life as Measured by FACT-Br Score - Functional Well-being Score

  Baseline, beginning of each cycle (each cycle is 28 days), and 1 month after completion of treatment (up to 13 months, median length of treatment 6 cycles - each cycle is 28 days (full range 2-12 cycles))

Study Arms (2)

Arm 1: Temozolomide morning

EXPERIMENTAL

* 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; Other: Functional Assessment of Cancer Therapy - Brain; Other: ActTrust Condor Instrument Watch

Arm 2: Temozolomide evening

EXPERIMENTAL

* 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; Other: Functional Assessment of Cancer Therapy - Brain; Other: ActTrust Condor Instrument Watch

Interventions

Temozolomide DRUG

-Given standard of care

Also known as: Temodar

Arm 1: Temozolomide morning; Arm 2: Temozolomide evening

Functional Assessment of Cancer Therapy - Brain OTHER

* 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.

Also known as: FACT-Br

Arm 1: Temozolomide morning; Arm 2: Temozolomide evening

ActTrust Condor Instrument Watch OTHER

-Will be required to wear 24 hours per day and will only be removed at specified data collection time points

Arm 1: Temozolomide morning; Arm 2: Temozolomide evening

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 35601970 DERIVED

Related Links

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

MeSH Terms

Conditions

Glioma; Glioblastoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Astrocytoma

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Milan Chheda
• Organization: Washington University School of Medicine

mchheda@wustl.edu

314-747-2712

Study Officials

• Milan Chheda, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: May 24, 2016
• Study Start: August 11, 2016
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: June 27, 2025
• Results First Posted: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)