Supratentorial Malignant Brain TumorPhase 1MR1-1NCT01009866
Study of Immunotoxin, MR1-1
A Phase 1 study testing MR1-1 in people with Supratentorial Malignant Brain Tumor, run by Darell D. Bigner, MD, PhD at 1 site in United States.
Trial summary
Purpose of the study: Primary Objective: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of MR1-1KDEL when delivered intracerebrally by convection-enhanced delivery (CED) in patients with supratentorial malignant brain tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Supratentorial Malignant Brain Tumor
- What is being tested?
- MR1-1
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Dec 2012
- 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
- Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable disease (>0.5cm).
- Patient will have completed some form of radiation therapy prior to toxin treatment.
- Karnofsky Performance score >70.
- The presence of the target antigen, EGFRvIII, must be identified on tumor tissue by immunohistochemistry.
- Platelet count > 100 x 109/L; PTT and PT < 120% of normal range.
- Creatinine < 120% of normal range.
- Total bilirubin, SGOT, SGPT,alkaline phosphatase < 300% of normal range.
Who cannot join
- Patients who are pregnant, breast-feeding, or unwilling to practice an effective method of birth control.
- Patients with known potentially anaphylactic allergic reactions to iodine or gadolinium-DTPA.
- Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods or plates).
- Patients that have not recovered from the toxic effects of prior chemotherapy and/or radiation therapy.
- Patients with an impending, life-threatening cerebral herniation syndrome.
- Patients with subependymal or CSF disease.
- Patients who are under the age of 18 years.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Health System
Durham, North Carolina, 27710
About this study
Official title: Phase I Study of Immunotoxin, MR1-1
Purpose of the study:
Primary Objective: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of MR1-1KDEL when delivered intracerebrally by convection-enhanced delivery (CED) in patients with supratentorial malignant brain tumors.
Read more
Secondary Objective: Document any radiographic responses associated with intracerebral CED of MR1-1KDEL.
Hypothesis: The investigators believe that MR1-1KDEL will be an effective anti-tumor agent for patients with supratentorial malignant brain tumors when delivered by CED.
Design \& procedures: This protocol is designed primarily to determine the MTD and DLT of a novel, tumor-specific immunotoxin, MR1-1KDEL. MR1-1KDEL will be delivered intracerebrally by CED using 2 intracerebral catheters with at least one catheter placed within the enhancing portion of the tumor. 124I-labeled albumin will be co-infused with gadolinium and PET and MRI images will be obtained at the conclusion of the infusion to monitor volume of drug distribution and leakage into the CSF space.
Based on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two to four catheters. A total of 144 mLs of drug solution will be delivered over 72 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg). At least 3 patients will be enrolled in each cohort. All patients in a given cohort will be observed for at least two weeks following infusion of the study drug before patients in the next cohort are treated. If no patients in a given cohort experience a DLT, the dose will be escalated in the next cohort. If 1 out of 3 patients in a given cohort experience DLT, 3 additional patients will be entered in that cohort. If 2 patients develop a DLT in any cohort of 3 or 6 patients, the previous dose will be declared the MTD. Patients will be followed at 1, 3, 6, 9, 12 month intervals for toxicity and adverse events, radiographic response, and survival. Patients will be off study when progressive disease is documented.
Risk/benefit assessment: This is an experimental study and unforeseeable or unexpected risks may be involved.
- Conditions
- Supratentorial Malignant Brain Tumor
- Being tested
- MR1-1
- Keywords
- Malignant brain tumor, GBM, recurrent brain tumor, Supratentorial malignant brain tumor, astrocytomas, ependymomas, Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable, disease (>0.5cm).
- Medical subject headings
- Brain Neoplasms, Astrocytoma, Ependymoma, Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR1-1Biological
Also called MR1-1KDEL
Based on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two catheters. A total of 96 mLs of drug solution will be delivered over 96 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg).
| Study group | Role | What they receive |
|---|---|---|
| MR1-1 | Experimental | All subjects are enrolled onto this arm. All subjects will receive MR1-1. Receives: Biological: MR1-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose and dose limiting toxicity
Measured: continual
Secondary outcomes (1)
Disease Progression
Measured: continual
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2009 (estimated)
- Study startNov 2006
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Supratentorial Malignant Brain TumorStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Darell D. Bigner, MD, PhD
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Sponsor-investigator, Darell D. Bigner, MD, PhD, Duke University
- Investigators
- Annick Desjardins, MD, Principal investigator, Duke Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01009866
- Sponsor's protocol ID
- Pro00011617
- Other IDs
- P50NS020023
- Acronym
- MR1-1
- Status last verified
- Mar 2015
- First submitted
- 6 Nov 2009
- Last updated
- 20 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Immunotoxin, MR1-1
- ClinicalTrials.gov ID
- NCT01009866
- Acronym / sponsor ID
- MR1-1 / Pro00011617
- Conditions
- Supratentorial Malignant Brain Tumor
- Keywords
- Malignant brain tumor, GBM, recurrent brain tumor, Supratentorial malignant brain tumor, astrocytomas, ependymomas, Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable, disease (>0.5cm).
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Darell D. Bigner, MD, PhDUniversity, hospital or other
- Collaborators
- National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Nov 2006
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 9 Nov 2009 (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.
Purpose of the study:
Primary Objective: Determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of MR1-1KDEL when delivered intracerebrally by convection-enhanced delivery (CED) in patients with supratentorial malignant brain tumors.
Secondary Objective: Document any radiographic responses associated with intracerebral CED of MR1-1KDEL.
Hypothesis: The investigators believe that MR1-1KDEL will be an effective anti-tumor agent for patients with supratentorial malignant brain tumors when delivered by CED.
Design \& procedures: This protocol is designed primarily to determine the MTD and DLT of a novel, tumor-specific immunotoxin, MR1-1KDEL. MR1-1KDEL will be delivered intracerebrally by CED using 2 intracerebral catheters with at least one catheter placed within the enhancing portion of the tumor. 124I-labeled albumin will be co-infused with gadolinium and PET and MRI images will be obtained at the conclusion of the infusion to monitor volume of drug distribution and leakage into the CSF space.
Based on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two to four catheters. A total of 144 mLs of drug solution will be delivered over 72 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg). At least 3 patients will be enrolled in each cohort. All patients in a given cohort will be observed for at least two weeks following infusion of the study drug before patients in the next cohort are treated. If no patients in a given cohort experience a DLT, the dose will be escalated in the next cohort. If 1 out of 3 patients in a given cohort experience DLT, 3 additional patients will be entered in that cohort. If 2 patients develop a DLT in any cohort of 3 or 6 patients, the previous dose will be declared the MTD. Patients will be followed at 1, 3, 6, 9, 12 month intervals for toxicity and adverse events, radiographic response, and survival. Patients will be off study when progressive disease is documented.
Risk/benefit assessment: This is an experimental study and unforeseeable or unexpected risks may be involved.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MR1-1 | Experimental | Biological: MR1-1All subjects are enrolled onto this arm. All subjects will receive MR1-1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Residual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurable disease (>0.5cm).
- Patient will have completed some form of radiation therapy prior to toxin treatment.
- Karnofsky Performance score >70.
- The presence of the target antigen, EGFRvIII, must be identified on tumor tissue by immunohistochemistry.
- Platelet count > 100 x 109/L; PTT and PT < 120% of normal range.
Key exclusion criteria (7 listed)
- Patients who are pregnant, breast-feeding, or unwilling to practice an effective method of birth control.
- Patients with known potentially anaphylactic allergic reactions to iodine or gadolinium-DTPA.
- Patients who cannot undergo MRI due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods or plates).
- Patients that have not recovered from the toxic effects of prior chemotherapy and/or radiation therapy.
- Patients with an impending, life-threatening cerebral herniation syndrome.
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 |
|---|---|---|
| MR1-1Also: MR1-1KDELBased on preclinical toxicity studies, the starting total drug dose will be 0.5μg (500ng) which represents 1/20th of the MTD in rats. The infusion flow rate will be fixed at 0.5 mL/h from each of two catheters. A total of 96 mLs of drug solution will be delivered over 96 hours. MR1-1KDEL dose escalation will be accomplished by increasing drug concentration allowing flow rate and infusion volume to remain unchanged. Drug dose will be doubled in successive cohorts so long as DLTs are not observed as follows: 25 ng/mL (2.4 μg)(starting dose); 50ng/mL (4.8μg); 100 ng/mL (9.6μg); 200ng/mL (19.2μg); 400 ng/mL (38.4μg); 800 ng/mL (76.8μg); and 1600 ng/mL (153.6μg). | Biological | MR1-1 |
Primary outcome
Maximum tolerated dose and dose limiting toxicity
Time frame: continual
1 secondary outcome
Disease Progression
Time frame: continual
Results and safety
The study was stopped early (reason given: low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Mar 2015.
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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.
Annick Desjardins, MD principal investigator
Duke Health
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 MR1-1 in people with Supratentorial Malignant Brain Tumor, run by Darell D. Bigner, MD, PhD 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 7 inclusion and 7 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: stopped early, as of the sponsor's last update on 20 Mar 2015. 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 was stopped early (reason given: low accrual). Results are not available in the source record.
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?
Maximum tolerated dose and dose limiting toxicity (time frame: continual). 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 20 Mar 2015.