Trials Sponsors Conditions Drugs Pricing

Brief 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. 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

Keywords

Malignant brain tumorGBMrecurrent brain tumorSupratentorial malignant brain tumorastrocytomasependymomasResidual, progressive, or recurrent supratentorial malignant brain tumor based on imaging studies with measurabledisease (>0.5cm).

Outcome Measures

Primary Outcomes (1)

Maximum tolerated dose and dose limiting toxicity
continual

Secondary Outcomes (1)

Disease Progression
continual

Study Arms (1)

MR1-1

EXPERIMENTAL

All subjects are enrolled onto this arm. All subjects will receive MR1-1.

Biological: MR1-1

Interventions

MR1-1Biological

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).

Also known as: MR1-1KDEL

MR1-1

Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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.

Sponsors & Collaborators

Darell D. Bigner, MD, PhD
Otherlead
National Institute of Neurological Disorders and Stroke (NINDS)
NIHcollaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

MeSH Terms

Conditions

Brain NeoplasmsAstrocytomaEpendymomaDisease

Condition Hierarchy (Ancestors)

Central Nervous System NeoplasmsNervous System NeoplasmsNeoplasms by SiteNeoplasmsBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesGliomaNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and Embryonal

Study Officials

Annick Desjardins, MD
Duke Health
PRINCIPAL INVESTIGATOR

Enrollment

9 participants (actual enrollment reported by the registry).

Study Design

Study Type: interventional
Phase: phase 1
Allocation: NA
Masking: NONE
Purpose: TREATMENT
Intervention Model: SINGLE GROUP
Sponsor Type: OTHER
Responsible Party: SPONSOR INVESTIGATOR
PI Title: Director, The Preston Robert Tisch Brain Tumor Center at Duke

Study Record Dates

First Submitted

November 6, 2009

First Posted

November 9, 2009

Study Start

November 2006

Date type not reported

This date has not been verified as actual or estimated.

Study Stopped

Study of Immunotoxin, MR1-1

Brief Summary

Registry Overview

Trial Relationships

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (1)

Study Arms (1)

MR1-1

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Source record

Locations

Study Stopped

Study of Immunotoxin, MR1-1

Brief Summary

Registry Overview

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (1)

Secondary Outcomes (1)

Study Arms (1)

MR1-1

Interventions

Eligibility Criteria

You may qualify if:

Sponsors & Collaborators

Study Sites (1)

MeSH Terms

Conditions

Condition Hierarchy (Ancestors)

Study Officials

Enrollment

Study Design

Study Record Dates

You may not qualify if:

Source record

Locations