- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02337426
Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. To determine the recommended phase 2 dose (RP2D) of dimethyl fumarate (DMF) when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed glioblastoma multiforme (GBM).
SECONDARY OBJECTIVES:
I. To evaluate the safety, tolerance, and toxicity of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.
II. To obtain a preliminary estimate of the efficacy of DMF when combined with standard concurrent temozolomide and RT in subjects with newly diagnosed GBM.
OUTLINE: This is a dose-escalation study of dimethyl fumarate.
CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide orally (PO) once daily (QD) for 42-49 days and dimethyl fumarate PO twice daily (BID) or thrice daily (TID) continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions.
MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days and then every 2 months thereafter.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Virginia
-
Richmond, Virginia, United States, 23298
- Virginia Commonwealth University/Massey Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histopathologically proven diagnosis of glioblastoma or gliosarcoma (World Health Organization [WHO] grade IV) following either a surgical resection or biopsy
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Subjects must have recovered from surgery or biopsy before study registration
- Therapy must begin between 21 days (3 weeks) and 42 days (6 weeks) after the most recent brain tumor surgery(resection or biopsy)
- Documentation of steroid doses 10-14 days prior to study registration and stable or decreasing steroid dose over the week prior to registration
- Absolute neutrophil count (ANC) >= 1500/mm^3
- Platelets >= 100,000/mm^3 (untransfused)
- Hemoglobin >= 10 g/dL (the use of transfusion or other intervention to achieve hemoglobin >= 10 g/dL is acceptable)
- Creatinine =< 1.5 x upper limit of normal (ULN) for the laboratory or calculated or actual creatinine clearance > 45 mL/min
- Total bilirubin =< 1.5 x ULN for the laboratory (total bilirubin criteria may be waived if a subject has documented Gilbert's syndrome)
- Aspartate aminotransferase (AST) =< 3 x ULN for the laboratory
- Alanine aminotransferase (ALT) =< 3 x ULN for the laboratory
- Women of childbearing potential and male subjects must practice adequate contraception
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- Prior invasive malignancy (except for non-melanoma skin cancer) unless disease free for >= 3 years
- Recurrent malignant gliomas
- Metastases detected below the tentorium or beyond the cranial vault
- Prior chemotherapy or radiation therapy (RT) for the diagnosis of GBM or for cancers of the head and neck
- Clinically significant cardiac disease, including major cardiac dysfunction, such as uncontrolled angina, clinical congestive heart failure with New York Heart Association (NYHA) class III or IV, ventricular arrhythmias requiring anti-arrhythmic therapy
- Pregnant or lactating women
- History of allergic reactions or intolerance to any of the required agents on the study
- History of hypersensitivity to dacarbazine
- Any treatment for GBM, other than surgery or anti-epileptic therapy, within 30 days prior to study treatment initiation
- Other condition(s) that in the opinion of the investigator might compromise the objectives of the study or increase patient risk
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (dimethyl fumarate, temozolomide, radiation therapy)
CONCOMITANT THERAPY: Between 21 days (3 weeks) and 42 days (6 weeks) following the last surgical procedure, patients receive temozolomide PO QD for 42-49 days and dimethyl fumarate PO BID or TID continuously. Patients also undergo radiation therapy 5 days a week over 6 weeks for a total of 30 fractions MAINTENANCE THERAPY: Patients continue to receive dimethyl fumarate PO BID or TID continuously. Four weeks after completing concomitant temozolomide and radiation therapy, patients also receive temozolomide PO QD on days 1-5. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. |
Undergo radiation therapy
Other Names:
Given PO
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
RP2D for DMF when combined with concurrent temozolomide and radiotherapy determined by the incidence of dose limiting toxicities (DLTs) graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0
Time Frame: Up to 6 weeks
|
Subjects' treatment dosing level, dose modification, DLTs, and evaluability for DLTs and response will be listed and summarized by basic descriptive statistics (such as frequency and proportion).
|
Up to 6 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events graded according to NCI CTCAE version 4.0
Time Frame: Up to 30 days after completion of treatment
|
Subjects' demographics, adverse events, serious adverse events, and treatment status will be listed and summarized by descriptive statistics (such as frequency, proportion, mean, standard deviation, median, and range).
|
Up to 30 days after completion of treatment
|
Progression free survival (PFS)
Time Frame: Time from registration to time of symptomatic and/or radiographic progression or death, whichever occurs first, assessed up to 2 years
|
The Kaplan-Meier method will be conducted to describe PFS, and median PFS will be estimated, along with 95% confidence intervals.
A Cox regression model may be used to model the PFS and adjusting for any effects of potential clinical characteristics.
|
Time from registration to time of symptomatic and/or radiographic progression or death, whichever occurs first, assessed up to 2 years
|
Overall survival (OS)
Time Frame: Time from registration until death from any cause, assessed up to 2 years
|
The Kaplan-Meier method will be conducted to describe OS, and median OS will be estimated, along with 95% confidence intervals.
A Cox regression model may be used to model the OS and adjusting for any effects of potential clinical characteristics.
|
Time from registration until death from any cause, assessed up to 2 years
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Response rate assessed as per the Response Assessment in Neuro-oncology for magnetic resonance imaging scans or Macdonald criteria for computed tomography scans
Time Frame: Up to 2 years
|
The clinical response rate will be calculated for each cohort, along with their corresponding 95% confidence intervals.
Logistic regression may be used to model the rate by adjusting potential clinical characteristics (such as age, gender, and tumor grade).
Mean and standard deviation of duration of response (overall response, complete response, and stable disease, respectively), along with its 95% confidence interval, will be estimated based on the method proposed by Ellis et al. via the exponential distribution.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mark G Malkin, MD, Massey Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Astrocytoma
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Glioblastoma
- Gliosarcoma
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Dermatologic Agents
- Temozolomide
- Dimethyl Fumarate
Other Study ID Numbers
- MCC-13-09950 (Other Identifier: Virginia Commonwealth University/Massey Cancer Center)
- P30CA016059 (U.S. NIH Grant/Contract)
- NCI-2014-02619 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- HM20003022
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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