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Temozolomide Chronotherapy for High Grade Glioma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02781792
Recruitment Status : Active, not recruiting
First Posted : May 24, 2016
Last Update Posted : October 10, 2022
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Description
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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
Glioma Glioblastoma Multiforme Drug: Temozolomide Other: Functional Assessment of Cancer Therapy - Brain Other: ActTrust Condor Instrument Watch Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Feasibility Study Evaluating Temozolomide Chronotherapy for High Grade Glioma
Actual Study Start Date : August 11, 2016
Estimated Primary Completion Date : July 14, 2024
Estimated Study Completion Date : July 14, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: Temodar

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 Name: FACT-Br

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 Name: Temodar

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 Name: FACT-Br

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
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Primary Outcome Measures :
  1. Feasibility of patient treatment compliance as measured by at least 80% compliance with assigned administration time [ Time Frame: 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.

  2. Duration of response [ Time Frame: Through completion of follow-up (estimated to be 30 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 :
  1. Number of patients experiencing grade 3 or 4 lymphopenia, thrombocytopenia, neutropenia and anemia in each group as measured by standard blood draws [ Time Frame: 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

  2. Quality of life as measured by FACT-Br score [ Time Frame: 1 month after completion of treatment (estimated to be 7 months) ]
  3. Progression-free survival (PFS) [ Time Frame: Through completion of follow-up (estimated to be 30 months) ]
    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  4. Overall survival [ Time Frame: Through completion of follow-up (estimated to be 30 months) ]
  5. 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 [ Time Frame: 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
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02781792


Locations
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United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
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Principal Investigator: Milan Chheda, M.D. Washington University School of Medicine
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02781792    
Other Study ID Numbers: 201605081
First Posted: May 24, 2016    Key Record Dates
Last Update Posted: October 10, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
 Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents