Convection Enhanced Localized Administration of PRX321 With Real-time Imaging for Therapy of Recurrent Glioblastoma (CLARITY-1)

NCT00797940 | Withdrawn Phase 2

• 1 other identifier: PRX321-1-05
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

A Phase II, multi-center, open-label, single-arm study in up to 42 subjects with first recurrence or progression of GBM at up to 12 sites in Australia, Europe, Israel, and the United States. Subjects will receive intratumoral infusion of PRX321 administered via convection-enhanced delivery (CED) at a concentration of 1.5 μg/mL and a total volume of 60 mL over 2 to 7 days. Primary Objective: To evaluate the efficacy (expressed as overall survival at 6 months \[OS-6\]) of intratumoral infusion of PRX321 in subjects with first recurrence or progression of glioblastoma multiforme (GBM). Secondary Objectives: To assess the safety of intratumoral infusion with PRX321 in subjects with recurrent or progressive GBM. To evaluate objective response rate (ORR), duration of response (DR), overall survival (OS), and progression-free survival (PFS). Tertiary Objective: To evaluate the relationship of observed infusate distribution with clinical and radiological responses.

Conditions

Glioblastoma Multiforme

Keywords

GBM; Glioblastoma; Glioblastoma Multiforme; Brain Tumor; Brain Cancer; Glioma

Outcome Measures

Primary Outcomes (1)

• To evaluate the efficacy (expressed as overall survival at 6 months [OS-6]) of intratumoral infusion of PRX321 in subjects with first recurrence or progression of glioblastoma multiforme (GBM)

  6 months

Secondary Outcomes (1)

• To evaluate objective response rate (ORR), duration of response (DR), overall survival (OS), and progression-free survival (PFS). To assess the safety of intratumoral infusion with PRX321 in subjects with recurrent or progressive GBM.

  Up to 24 months

Study Arms (1)

Single Arm

EXPERIMENTAL

Up to 42 subjects with first recurrence or progression of GBM

Drug: IL-4PE

Interventions

IL-4PE DRUG

Subjects will receive intratumoral infusion of PRX321 administered via convection-enhanced delivery (CED) at a concentration of 1.5 μg/mL and a total volume of 60 mL over 2 to 7 days.

Also known as: PRX321

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects at least 18 years old
• GBM at first recurrence or progression (i.e., disease progressed after any first-line therapy including surgery and radiotherapy as confirmed by MR imaging \[MRI\]); screening MRIs used to confirm eligibility must be available to the Investigator and the Independent Review Committee (IRC)
• Unilateral, unifocal, and supratentorial tumor, with a maximum diameter of 4 cm (i.e., maximum distance between the borders/edges of enhancing regions) visualized in any arbitrary imaging plane, as assessed by the IRC on MRI taken pre-study 2 weeks prior to catheter placement
• Histological confirmation of GBM (confirmation before primary therapy is acceptable)
• KPS ≥ 70
• If female of childbearing potential, an acceptable method of contraception must be combined with negative pregnancy test before entering the study and must be willing to use contraception for 2 months after treatment with PRX321; male subjects who are non-sterile (i.e., male who has not been sterilized by vasectomy for at least 6 months) must be willing to use a barrier method of contraception for at least 2 months after treatment with PRX321. Acceptable methods of contraception are:
• intra-uterine contraceptive device without hormone release system: placed at least 4 weeks prior to treatment with PRX321;
• simultaneous use of male condom and diaphragm + spermicide: starting at least 14 days prior to treatment with PRX321; or
• simultaneous use of male condom and female condom + spermicide: starting at least 14 days prior to treatment with PRX321
• Able to read, understand, and sign the informed consent document before undergoing any study-specific procedures or have a legal representative willing to do so
• Able and willing to undergo multiple MRI examinations
• Able and willing to comply with all study procedures

You may not qualify if:

• A tumor in the brain stem (not including fluid attenuation inversion recovery \[FLAIR\] changes), an infratentorial tumor, or multifocal satellite tumors
• Tumor with a clinically significant mass effect (\> 5 mm midline shift) while on a stable corticosteroid dose
• Subjects with tumors that are completely liquefied (cystic or ring enhancement) in which convection would not be possible
• Tumor with geometric features that make them difficult to adequately cover the tumor volume with infusate by using CED catheters; these tumors include the following:
• Tumors that appear to wrap around ventricular structures, such that the catheter tips may be positioned within 1.0 cm of a ventricle or such that a large angle (such as an "elbow" or "L- shape") in the tumor shape is present and convection is likely to be compromised;
• Tumors in which post-surgical enhancement in T1 images in the margins around a resection cavity may be confused with recurring tumor; subjects in whom this enhancement exceeds 5 mm thickness are excluded
• Clinical symptoms that are thought by the Investigator to be caused by uncontrolled increased intracranial pressure, hemorrhage, or edema of the brain
• Inadequate organ function, defined as 1 or more of the following:
• Hemoglobin \< 9.0 g/dL (support with therapeutic erythropoietin products is acceptable);
• Absolute neutrophil count (ANC) \< 1500/mm3 (unsupported by colony stimulating factors);
• Platelet count \< 100,000/mm3 (unsupported by colony stimulating factors);
• Total bilirubin \> 2.0 x upper limit of normal (ULN);
• Alanine transaminase (ALT) and aspartate transaminase (AST) \> 3.0 x ULN;
• Prothrombin time (PT)/international normalized ratio (INR) \> 1.5;
• Creatinine \> 3.0 x ULN;

Sponsors & Collaborators

• Sophiris Bio Corp: lead

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Glioma

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2008
• First Posted: November 25, 2008
• Study Start: January 1, 2009
• Primary Completion: December 1, 2010
• Last Updated: December 3, 2012

Record last verified: 2012-11