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| BRAINLIFE NEWSLETTER | |
Volume 3, Number 37 - 5 October 2004 |
|
| Clincal Trial Information |
Phase III Study of Therapy with TransMID™ (Tf-CRM107) Compared to Best Standard of Care in Patients with Glioblastoma Multiforme
The
clinical trial (Trial Lead
Organization: Xenova Group plc) is designed to enrol 323
patients with non-resectable, progressive or recurrent Glioblastoma Multiforme
(GBM) who have failed conventional therapy.
The study will be a randomised, open-labelled, multi-centre trial and will
compare TransMID™
against a number of presently used chemotherapeutic agents
regarded as "best standard of care" (BSC).
The 323 patients will be randomised in a 2:1 ratio of
TransMID™:BSC across
approximately 50 sites in the EU, Israel and North America.
The
primary end-point is overall survival time with a planned interim analysis to be
conducted after 50% of the required events have been observed.
TransMID™
is a modified diphtheria toxin conjugated to transferrin.
When TransMID™
binds to transferrin receptors on the surface of the cell, the
diphtheria toxin gains entry to the cell.
Once inside the cell, the diphtheria toxin interferes with protein synthesis and
ultimately kills the cell.
Transferrin receptors are particularly prevalent on rapidly dividing cells, and
the high level of transferrin receptor expression on glioma cells relative to
normal brain tissue makes transferrin an appropriate targeting mechanism for the
diseased cells.
TransMID™
is pumped directly into the brain tumour using CED (Convection Enhanced
Delivery).
In
a Phase II study, 50% or greater reduction in tumour volume was noted in 35% of
evaluable patients, with a corresponding increase in life expectancy in those
patients that did respond.
Median survival time for patients receiving TransMID™
was approximately 37 weeks.
This compares to the average life expectancy of approximately 26 weeks for
patients with this condition being treated with best standard of care.
| References |
Laske DW, Ilercil O, Akbasak A, Youle RJ, Oldfield EH
Efficacy of direct intratumoral
therapy with targeted protein toxins for solid human gliomas in nude mice
J Neurosurg, 1994 Mar;80(3):520-6. (Laboratory Investigation, Abstract)
Laske
DW, Youle RJ, Oldfield EH
Tumor regression
with regional distribution of the targeted toxin TF-CRM107 in patients with
malignant brain tumors
Nat
Med, 1997 Dec;3(12):1362-8 (Clinical Study, Abstract)
Hagihara N, Walbridge S, Olson AW, Oldfield EH, Youle
RJ
Vascular protection by
chloroquine during brain tumor therapy with Tf-CRM107
Cancer Res, 2000 Jan 15;60(2):230-4. (Laboratory Investigation, Abstract
& Full Text)
M.
Weaver, D.W. Laske
Transferrin Receptor Ligand-Targeted Toxin
Conjugate (Tf-CRM107) for Therapy of Malignant Gliomas
J
Neurooncol,
October
2003, Volume 65, Number 1, Pages 3 -- 14 (Clinical
Study, Abstract
& Notes)
| Protocol Synopsis |
As
supplied by the Trial Lead
Organization.
Record first received: 1 October 2004.
| STUDY NO: | KSB311R/CIII/001 |
| TITLE: | A Phase III multicenter study of intratumoral/interstitial therapy with TransMID™ compared to best standard of care in patients with progressive and/or recurrent, non-resectable glioblastoma multiforme. |
| SPONSOR: | Xenova Biomedix Ltd., 957 Buckingham Avenue, Slough, Berkshire, SL1 4NL, UK. Tel: +44 1753 706600. |
| REGULATORY STATUS: | Open IND (BB6452); Orphan Drug Status in USA and EU; Fast Track Designation in the US. |
| STUDY OBJECTIVES: |
Primary objective:
Secondary objectives:
|
| STUDY DESIGN: | Multicenter,
open label, randomized study comparing TransMID™
with a chemotherapeutic regimen considered to be best standard of care and
consisting of either nitrosoureas, platinum compounds, temozolomide,
procarbazine or PCV (procarbazine, lomustine (CCNU) & vincristine). A planned interim analysis of the primary efficacy endpoint will be conducted after approximately 50% of the required events have been observed. |
| STUDY POPULATION | |
| Number of Patients: |
Total: 323 Patients TransMID™: 215 (accounting for drop-outs) Best standard of care: 108 (accounting for drop-outs). |
| Number of groups: | Two; randomization ratio 2 TransMID™ to 1 best standard of care; stratified on baseline Karnofsky score (≤80 vs >80) and age (≤40 years vs >40 years). |
| Age/Sex: | At least 18 years old, male and female. |
| Study specific requirements: | Patients diagnosed with glioblastoma multiforme which has been confirmed histologically and who have undergone conventional treatment, including surgery (biopsy or debulking) and/or radiation therapy and/or chemotherapy, who have a recurrent and/or progressive tumor ≥1.0 cm and ≤4.0 cm in diameter. |
| INVESTIGATIONAL PRODUCT | |
| Route of administration: | Directly into the tumor via two silastic catheters. |
| Dosage(s) and frequency: | 0.67 µg/mL at a rate of up to 0.20 mL/hour through each catheter to a maximum of 40 mL, giving a total dose of 26.8 µg per treatment. |
| Duration of dosing (days): | Each
patient will receive two doses of TransMID™, providing the first is
tolerated, separated by 4-8 weeks. Each infusion will take 4-7 days. |
| COMPARATOR PRODUCT: | For the best standard of care arm, the usual dosage regimen used by the hospital should be followed. |
| EVALUATION CRITERIA | |
| Efficacy: |
Primary:
Secondary:
|
| Safety: |
|
| Other: |
|
| ANTICIPATED STUDY DATES | |
| Start of clinical phase: | Q2 2004 |
| Completion of clinical phase: | Q3 2006 |
| Location and Contact Information |
ClinicalTrials.gov
http://www.clinicaltrials.gov/ct/show/NCT00083447?order=2
National
Cancer Institute
http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=373837&protocolsearchid=1030238&version=healthprofessional
Virtualtrials.com
http://virtualtrials.com/trialdetails.cfm?id=122800628