Adult Brain GlioblastomaPhase 1NCT02337426
Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
A Phase 1 study testing Dimethyl Fumarate, Temozolomide and Radiation Therapy in people with Adult Brain Glioblastoma and Adult Giant Cell Glioblastoma, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Brain Glioblastoma, Adult Giant Cell Glioblastoma, Adult Gliosarcoma
- What is being tested?
- Dimethyl Fumarate, Temozolomide and Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2015to 9 Nov 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University/Massey Cancer Center
Richmond, Virginia, 23298
About this study
Official title: Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme
This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Dimethyl fumarate may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving dimethyl fumarate with temozolomide and radiation therapy may work better in treating glioblastoma multiforme.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Being tested
- Dimethyl Fumarate, Temozolomide, Radiation Therapy
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dimethyl FumarateDrug
Also called Fumaric Acid, Dimethyl Ester
Given PO
TemozolomideDrug
Also called TMZ
Given PO
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation
Undergo radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Treatment (dimethyl fumarate, temozolomide, radiation therapy) | Experimental | 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. Receives: Drug: Dimethyl Fumarate; Drug: Temozolomide; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
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).
Measured: Up to 6 weeks
Secondary outcomes (4)
Incidence of adverse events graded according to NCI CTCAE version 4.0
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).
Measured: Up to 30 days after completion of treatment
Progression free survival (PFS)
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.
Measured: Time from registration to time of symptomatic and/or radiographic progression or death, whichever occurs first, assessed up to 2 years
Overall survival (OS)
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.
Measured: Time from registration until death from any cause, assessed up to 2 years
Response rate assessed as per the Response Assessment in Neuro-oncology for magnetic resonance imaging scans or Macdonald criteria for computed tomography scans
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.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2015 (estimated)
- Study start13 Feb 2015
- Primary completion8 Nov 2016
- Study completion9 Nov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Brain GlioblastomaStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Mark G Malkin, MD, Principal investigator, Massey Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02337426
- Sponsor's protocol ID
- MCC-13-09950
- Other IDs
- NCI-2014-02619, HM20003022, MCC-13-09950, P30CA016059
- Status last verified
- Jun 2019
- First submitted
- 8 Jan 2015
- Last updated
- 28 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Dimethyl Fumarate, Temozolomide, and Radiation Therapy in Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT02337426
- Acronym / sponsor ID
- MCC-13-09950
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 13 Feb 2015 (actual)
- Primary completion
- 8 Nov 2016 (actual)
- Study completion
- 9 Nov 2017 (actual)
- First posted
- 13 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 1 trial studies the side effects and best dose of dimethyl fumarate when given together with temozolomide and radiation therapy(RT) in treating patients with newly diagnosed glioblastoma multiforme (GBM). Dimethyl fumarate may help radiation therapy work better by making tumor cells more sensitive to the radiation therapy. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving dimethyl fumarate with temozolomide and radiation therapy may work better in treating glioblastoma multiforme.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (dimethyl fumarate, temozolomide, radiation therapy) | Experimental | Drug: Dimethyl Fumarate, Drug: Temozolomide, Radiation: Radiation TherapyCONCOMITANT 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dimethyl FumarateAlso: Fumaric Acid, Dimethyl EsterGiven PO | Drug | Treatment (dimethyl fumarate, temozolomide, radiation therapy) |
| TemozolomideAlso: TMZGiven PO | Drug | Treatment (dimethyl fumarate, temozolomide, radiation therapy) |
| Radiation TherapyAlso: Cancer Radiotherapy, Irradiate, Irradiated, IrradiationUndergo radiation therapy | Radiation | Treatment (dimethyl fumarate, temozolomide, radiation therapy) |
Primary outcome
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).
4 secondary outcomes
Incidence of adverse events graded according to NCI CTCAE version 4.0
Time frame: 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
Overall survival (OS)
Time frame: Time from registration until death from any cause, assessed up to 2 years
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark G Malkin, MD principal investigator
Massey Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dimethyl Fumarate, Temozolomide and Radiation Therapy in people with Adult Brain Glioblastoma and Adult Giant Cell Glioblastoma, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jun 2019.