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Temozolomide Chronotherapy for High Grade Glioma

This study is currently recruiting participants.
Verified September 2017 by Washington University School of Medicine
Sponsor:
ClinicalTrials.gov Identifier:
NCT02781792
First Posted: May 24, 2016
Last Update Posted: September 28, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Washington University School of Medicine
  Purpose

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 Intervention Phase
Glioma Glioblastoma Multiforme Drug: Temozolomide Other: Functional Assessment of Cancer Therapy - Brain Phase 1

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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.

  • Duration of response [ Time Frame: Until disease progression (estimated to be 6 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:
  • 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

  • Quality of life as measured by FACT-Br score [ Time Frame: 2 months after completion of treatment (estimated to be 8 months) ]
  • Progression-free survival (PFS) [ Time Frame: Until disease progression (estimated to be 6 months) ]
    PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  • Overall survival [ Time Frame: Until patient death (estimated to be 15 months) ]

Estimated Enrollment: 30
Actual Study Start Date: August 11, 2016
Estimated Study Completion Date: November 30, 2019
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 2 months 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)
Other Name: FACT-Br
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 2 months 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)
Other Name: FACT-Br

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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
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


Contacts
Contact: Jian Campian, M.D., Ph.D. (314) 747-4241 campian.jian@wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jian Campian, M.D., Ph.D.    314-747-4241    campian.jian@wustl.edu   
Principal Investigator: Jian Campian, M.D., Ph.D.         
Sub-Investigator: Katherine Weilbaecher, M.D.         
Sub-Investigator: Joshua Rubin, M.D., Ph.D.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Jian Campian, M.D., Ph.D. Washington University School of Medicine
  More Information

Additional Information:
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02781792     History of Changes
Other Study ID Numbers: 201605081
First Submitted: May 20, 2016
First Posted: May 24, 2016
Last Update Posted: September 28, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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:
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
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents