GlioblastomaPhase 2NCT04874506
MBM-02 (Tempol) for the Treatment of Glioblastoma Multiforme (GBM)
A Phase 2 study testing MBM-02 in people with Glioblastoma and Glioblastoma Multiforme, run by Matrix Biomed, Inc. at 1 site in United States.
Trial summary
MBM-02 (Tempol) is an HIF-1 and HIF-2 inhibitor that is being tested as an addition to standard of care treatment that includes radiotherapy and TMZ. MBM-02's ability to increase progression free survival and decrease side effects of TMZ and radiotherapy treatment will be assessed. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Glioblastoma, Glioblastoma Multiforme
- What is being tested?
- MBM-02
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2021to Aug 2023
- Phase
- Phase 2
- 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 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be > 35 and ≤ 75 years of age;
- Be newly diagnosed with glioblastoma multiforme within 4 weeks of open biopsy/resection;
- Be histologically confirmed to have definitive GBM by partial or complete surgical resection (i.e. not by biopsy only) within 4 weeks prior to MBM-02 administration;
- Have recovered from the effects of surgery, post-operative infection, and other complications before study registration;
- Have a diagnostic contrast-enhanced MRI or CT scan of the brain performed preoperatively and postoperatively prior to the initiation of radiotherapy, within 28 days prior to MBM-02 administration;
- If female and of child bearing potential, must be using an effective birth-control method as described in section 3.5;
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- If a male with a female partner of child bearing potential, adequate methods of contraception must be employed as described in section 3.5.
- If male, no sperm donation for 90 days until after the conclusion of the study;
- Be properly informed of the nature and risks of the clinical investigation, comply with all clinical investigation-related procedures, and sign an Informed Consent Form prior to entering the clinical investigation;
- Be able to participate for the full term of the clinical investigation;
- Have a Karnofsky performance status of >70;
- Have a life expectancy ≥ 6 months; and
- Have adequate baseline organ function (hematologic, liver, renal, nutritional and metabolic):
- Hematology:
- Absolute neutrophil count (ANC) ≥1.5 Hemoglobin ≥ 10 g/dL Platelets ≥ 100,000 per microliter of blood
- Hepatic:
- Total bilirubin ≤ 2 x ULN Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2 x ULN
- Renal:
- creatinine clearance (CrCl) ≥ 60 ml/min within 2 weeks prior to registration determined by 24-hour collection or estimated by Cockcroft-Gault formula: CrCl male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CrCl female = 0.85 x (CrCl male)
Who cannot join
- Evidence of recurrent GBM or metastases detected outside of the cranial vault;
- Patients with histone H3 K27M mutation or gliosarcoma;
- Patients using the Optune device during study drug administration;
- Prior cancer diagnosis other than skin basal cell or squamous cell carcinoma (non-metastatic);
- Patients unable to undergo MRI because of non-compatible devices;
- Oxygen dependent chronic obstructive pulmonary disease (COPD);
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- Unstable coronary artery disease (CAD);
- Diagnosis of midline diffuse glioma (glioblastoma);
- Insufficient biopsy tissue for full molecular profiling of the tumor;
- Prior radiation or chemotherapy for glioblastoma or glioma;
- Prior radiation for cancer of the head and neck that would result in an overlap of radiation fields;
- Evidence of a significant medical illness, or a psychiatric illness/social situation that would, in the investigator's judgment, make the patient inappropriate for this study;
- Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel resection that would preclude adequate absorption of the study drug;
- Have had a recent, serious, non-malignant medical complication that, in the opinion of the investigator, makes the individual unsuitable for study participation;
- Have used an investigational drug within 28 days of the initiation of study treatment;
- Have a history of a positive blood test for HIV;
- At the time of screening, have a significant active medical illness which, in the opinion of the investigator, would preclude completion of the study; and
- Body weight less than 35 kg (77 lbs.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Georgetown
Washington D.C., District of Columbia, 20007
Joseph Watson
Joseph Watson, MD
About this study
Official title: An Open Label Study to Assess the Safety and Clinical Efficacy of MBM-02 to Increase Survival in Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)
MBM-02 (Tempol) is an HIF-1 and HIF-2 inhibitor that is being tested as an addition to standard of care treatment that includes radiotherapy and TMZ. MBM-02's ability to increase progression free survival and decrease side effects of TMZ and radiotherapy treatment will be assessed.
Read the detailed description
MBM-02 is an HIF-1 and HIF-2 inhibitor that has shown in animal models to turn back on the apoptosis process (cell death) in cancer.
Hypoxia is well documented in most solid tumors (Vaupel et al., 1991). Acute, intermittent, and cycling hypoxia are associated with inadequate blood flow, whereas chronic hypoxia is the consequence of increased oxygen diffusion distance resulting from tumor expansion (Dewhirst et al., 2008). A study by Chen and colleagues (2015) showed that cycling hypoxia and chronic hypoxia are important tumor microenvironment phenomena that limit tumor response to chemotherapy in GBM.
In hypoxic conditions observed in solid state tumors, the hypoxia inducible factors, HIF-1α and HIF-2α, are upregulated and transcribe a panel of genes associated with cancer survival and progression, such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). These factors are essential for tumor survival, thereby increasing tumor progression and decreasing apoptosis. Without the functions of the HIF family of genes, solid-state tumors could not progress and would not survive. In both Chen et al. (2015) and Sourbier et al. (2012), researchers established that the active compound in MBM-02 is an inhibitor of both HIF-1α and HIF-2α.
This is an open label multisite trial that will assess MBM-02's ability to increase progress free survival in patients receiving standard of care for glioblastoma.
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Being tested
- MBM-02
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MBM-02Drug
Also called Tempol; 4-hydroxy-tempo; 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl
Study drug will be administered orally using the capsule formulation (200 mg). The study drug will be administered 7 days a week for the entire treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Cohort 1 will receive standard of care concomitantly with1000 mg/day of MBM-02.
Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods:
1. 1 week run-in with MBM-02 prior to radiotherapy;
2. 6 weeks of radiotherapy and concomitant temozolomide;
3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and
4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. Receives: Drug: MBM-02 |
| Cohort 2 | Experimental | Cohort 2 will receive standard of care concomitantly with1200 mg/day of MBM-02.
Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods:
1. 1 week run-in with MBM-02 prior to radiotherapy;
2. 6 weeks of radiotherapy and concomitant temozolomide;
3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and
4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. Receives: Drug: MBM-02 |
| Cohort 3 | Experimental | Cohort 2 will receive standard of care concomitantly with1400 mg/day of MBM-02.
Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods:
1. 1 week run-in with MBM-02 prior to radiotherapy;
2. 6 weeks of radiotherapy and concomitant temozolomide;
3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and
4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. Receives: Drug: MBM-02 |
| Cohort 4 | Experimental | Cohort 2 will receive standard of care concomitantly with1400 mg/day of MBM-02.
Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods:
1. 1 week run-in with MBM-02 prior to radiotherapy;
2. 6 weeks of radiotherapy and concomitant temozolomide;
3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and
4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. Receives: Drug: MBM-02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
Clinical efficacy as measured by progression-free survival rate at six months (PFS-6). Progression-free survival will be defined as the number of days from the date of first dose to the date of earliest disease progression based on RANO criteria.
Measured: baseline to 6 months
Secondary outcomes (3)
Overall Survival
Clinical efficacy as measured by the Overall Survival (OS) rate at 12 months, 18 months, and 24 months.
Measured: baseline to 24 months
Thrombocytopenia
Reduction in thrombocytopenia as measured by platelet count.
Measured: baseline to 12 months
Neutropenia
Reduction in neutropenia as measured by absolute neutrophil count
Measured: baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2021
- Study start1 Jun 2021 (estimated)
- Primary completionJan 2023 (estimated)
- Study completionAug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Three dosing regimens will be explored and represented by Cohort 1, Cohort 2, and Cohort 3. The first 6 patients (Cohort 1) will begin with a total daily dose (TDD) of 1000 mg of MBM-02.
- Masking
- None (open label)
- Enrolment
- 55 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Matrix Biomed, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- MedStar Health
- Responsible party
- Sponsor
- Investigators
- Joseph Watson, M.D., Principal investigator, Georgetown University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04874506
- Sponsor's protocol ID
- MBI-10-01
- Status last verified
- May 2021
- First submitted
- 3 May 2021
- Last updated
- 5 May 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Study to Assess the Safety and Clinical Efficacy of MBM-02 to Increase Survival in Patients With Newly Diagnosed Glioblastoma Multiforme (GBM)
- ClinicalTrials.gov ID
- NCT04874506
- Acronym / sponsor ID
- MBI-10-01
- Conditions
- Glioblastoma, Glioblastoma Multiforme
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 55 participants (estimated)
- Lead sponsor
- Matrix Biomed, Inc.Industry (pharma, biotech, devices)
- Collaborators
- MedStar Health
- Study start
- 1 Jun 2021 (estimated)
- Primary completion
- Jan 2023 (estimated)
- Study completion
- Aug 2023 (estimated)
- First posted
- 5 May 2021 (actual)
- 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.
MBM-02 (Tempol) is an HIF-1 and HIF-2 inhibitor that is being tested as an addition to standard of care treatment that includes radiotherapy and TMZ. MBM-02's ability to increase progression free survival and decrease side effects of TMZ and radiotherapy treatment will be assessed.
Detailed description
MBM-02 is an HIF-1 and HIF-2 inhibitor that has shown in animal models to turn back on the apoptosis process (cell death) in cancer.
Hypoxia is well documented in most solid tumors (Vaupel et al., 1991). Acute, intermittent, and cycling hypoxia are associated with inadequate blood flow, whereas chronic hypoxia is the consequence of increased oxygen diffusion distance resulting from tumor expansion (Dewhirst et al., 2008). A study by Chen and colleagues (2015) showed that cycling hypoxia and chronic hypoxia are important tumor microenvironment phenomena that limit tumor response to chemotherapy in GBM.
In hypoxic conditions observed in solid state tumors, the hypoxia inducible factors, HIF-1α and HIF-2α, are upregulated and transcribe a panel of genes associated with cancer survival and progression, such as vascular endothelial growth factor receptor (VEGFR), platelet derived growth factor (PDGF), and glucose transporter 1 (GLUT1). These factors are essential for tumor survival, thereby increasing tumor progression and decreasing apoptosis. Without the functions of the HIF family of genes, solid-state tumors could not progress and would not survive. In both Chen et al. (2015) and Sourbier et al. (2012), researchers established that the active compound in MBM-02 is an inhibitor of both HIF-1α and HIF-2α.
This is an open label multisite trial that will assess MBM-02's ability to increase progress free survival in patients receiving standard of care for glioblastoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Three dosing regimens will be explored and represented by Cohort 1, Cohort 2, and Cohort 3. The first 6 patients (Cohort 1) will begin with a total daily dose (TDD) of 1000 mg of MBM-02.
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: MBM-02Cohort 1 will receive standard of care concomitantly with1000 mg/day of MBM-02. Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods: 1. 1 week run-in with MBM-02 prior to radiotherapy; 2. 6 weeks of radiotherapy and concomitant temozolomide; 3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and 4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. |
| Cohort 2 | Experimental | Drug: MBM-02Cohort 2 will receive standard of care concomitantly with1200 mg/day of MBM-02. Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods: 1. 1 week run-in with MBM-02 prior to radiotherapy; 2. 6 weeks of radiotherapy and concomitant temozolomide; 3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and 4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. |
| Cohort 3 | Experimental | Drug: MBM-02Cohort 2 will receive standard of care concomitantly with1400 mg/day of MBM-02. Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods: 1. 1 week run-in with MBM-02 prior to radiotherapy; 2. 6 weeks of radiotherapy and concomitant temozolomide; 3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and 4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. |
| Cohort 4 | Experimental | Drug: MBM-02Cohort 2 will receive standard of care concomitantly with1400 mg/day of MBM-02. Patients will receive standard of care treatment for newly diagnosed Glioblastoma multiforme consisting of four sequential periods: 1. 1 week run-in with MBM-02 prior to radiotherapy; 2. 6 weeks of radiotherapy and concomitant temozolomide; 3. 4 weeks of rest post-radiotherapy and concomitant temozolomide; and 4. Adjuvant temozolomide treatment post 4-week rest period. Patients will be administered daily MBM-02 during all four sequential periods. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Be > 35 and ≤ 75 years of age;
- Be newly diagnosed with glioblastoma multiforme within 4 weeks of open biopsy/resection;
- Be histologically confirmed to have definitive GBM by partial or complete surgical resection (i.e. not by biopsy only) within 4 weeks prior to MBM-02 administration;
- Have recovered from the effects of surgery, post-operative infection, and other complications before study registration;
- Have a diagnostic contrast-enhanced MRI or CT scan of the brain performed preoperatively and postoperatively prior to the initiation of radiotherapy, within 28 days prior to MBM-02 administration;
Key exclusion criteria (18 listed)
- Evidence of recurrent GBM or metastases detected outside of the cranial vault;
- Patients with histone H3 K27M mutation or gliosarcoma;
- Patients using the Optune device during study drug administration;
- Prior cancer diagnosis other than skin basal cell or squamous cell carcinoma (non-metastatic);
- Patients unable to undergo MRI because of non-compatible devices;
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 |
|---|---|---|
| MBM-02Also: Tempol; 4-hydroxy-tempo; 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxylStudy drug will be administered orally using the capsule formulation (200 mg). The study drug will be administered 7 days a week for the entire treatment period. | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Progression Free Survival
Time frame: baseline to 6 months
Clinical efficacy as measured by progression-free survival rate at six months (PFS-6). Progression-free survival will be defined as the number of days from the date of first dose to the date of earliest disease progression based on RANO criteria.
3 secondary outcomes
Overall Survival
Time frame: baseline to 24 months
Thrombocytopenia
Time frame: baseline to 12 months
Neutropenia
Time frame: baseline to 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2021.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Joseph Watson, M.D. principal investigator
Georgetown University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MBM-02 in people with Glioblastoma and Glioblastoma Multiforme, run by Matrix Biomed, Inc. 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 19 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 5 May 2021. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Benji Crane (6264376506, bjcrane@matrixbiomed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (time frame: baseline to 6 months). 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 5 May 2021.