Study of Immunotoxin, MR1-1

NCT01009866 | Terminated Phase 1

• 2 other identifiers: Pro00011617P50NS020023
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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 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).

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

MR1-1 BIOLOGICAL

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Darell D. Bigner, MD, PhD: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Astrocytoma; Ependymoma; Disease

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Annick Desjardins, MD

  Duke Health

  PRINCIPAL INVESTIGATOR

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 1, 2006
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: March 20, 2015

Record last verified: 2015-03

Locations

US (1)