Targeted Toxins (Immunotoxins) for inoperable or recurrent glioblastomas

Targeted Toxins (Immunotoxins) for inoperable or recurrent glioblastoma
http://clinicaltrials.gov/ct/show/NCT00083447
TransMID is a drug that is a combination of a protein called transferrin
and a poison called diphtheria toxin.
Total Enrollment: 323
Study start: May 2004; Study completion: June 2007
Study of Therapy With TransMID? Compared to Best Standard of Care in
Patients With Glioblastoma Multiforme

http://www.gbmtrial.com/eligible.html
Inclusion and exclusion criteria outlined below.

INCLUSION CRITERIA INCLUDE (BUT ARE NOT LIMITED TO):
? Male or female at least 18 years of age
? Diagnosed GBM
? Progressive and/or recurrent GBM after conventional therapy
? Patient is not considered a candidate for surgery
? Karnofsky Performance Score 70-100
? Tumour characteristic must be:
? Unifocal Arising from or occurring in a single location.
? Unilateral Having to do with one side of the body.
? Lesion diameter equal to or greater than 1.0 cm and equal to or
less than 4.0 cm

EXCLUSION CRITERIA INCLUDE (BUT ARE NOT LIMITED TO):
? Chemotherapy within 30 days prior to study entry, or nitrosoureas or
Mitomycin-C therapy within 42 days prior to study entry
? Radiotherapy or stereotactic (gamma knife) radiosurgery within 90 days
prior to
study entry
? Tumour surgery, tumour debulking or other neurosurgery procedure within
30 days prior to study entry

Other clinical trials were:
http://clinicaltrials.gov/ct/show/NCT00088400
Completed Total Enrollment: 30
Study start: July 2004; Study completion: November 2005
Phase III
Comparison of TransMID vs Standard Treatment of Cancerous Brain Tumors
Condition: Glioblastoma
Primary Objective:

To evaluate the efficacy of intratumoral/interstitial therapy with
TransMID compared to best standard of care in patients with progressive
and/or recurrent, non-resectable glioblastoma multiforme.

Secondary Objectives:

To assess the safety of intratumoral/interstitial therapy with TransMID
compared to best standard of care in patients with progressive and/or
recurrent, non-resectable glioblastoma multiforme.

To evaluate possible differences in efficacy and/or safety with TransMID
associated with differing degrees of transferrin receptor expression in
tumor tissue and serum anti-diphtheria toxin antibody titer levels.


http://clinicaltrials.gov/ct/show/NCT00052624
Immunotoxin Therapy in Treating Children With Progressive or Recurrent
Glioblastoma Multiforme or Anaplastic Astrocytoma
No longer recruiting
Immunotoxin Therapy in Treating Children With Progressive or Recurrent
Glioblastoma Multiforme or Anaplastic Astrocytoma Phawe I Drug:
transferrin-CRM107
Condition: Brain and Central Nervous System Tumors
Official Title: A Phase I Multicenter Trial Of Intratumoral/Interstitial
Therapy With HN66000, NC66000 (TransMID) In Patients Between 5 and 18
Years Of Age With Progressive Or Recurrent Glioblastoma Multiforme Or
Anaplastic Astrocytoma
OUTLINE: This is a dose-escalation, open-label, multicenter study.
Patients are assigned to 1 of 2 treatment groups by age (5-9 vs 10-18).

All patients undergo stereotactic radiosurgery for tumor biopsy and
placement of 2 intratumoral silastic infusion catheters pre-loaded with
transferrin-CRM107 (Tf-CRM107).
Patients are followed monthly for 6 months and then every 3 months for 6
months.

http://www.philly.com/inquirer/special/cancer/6896112.html

Since 1992 TransMid has been in the development "pipelines" of eight
companies: Sterling Winthrop, Nycomed (merging and unmerging with IVAX),
Amersham, Intelligene Expressions, KS Biomedix and Xenova. In the fall,
Xenova was acquired by Celtic Pharma, based in Bermuda.

As rights to the drug were sold again and again, workers were laid off.
When Intelligene took over, Rossi was the only employee asked to stay.

While he's glad to still be on the TransMid team, the chain of owners has
been frustrating. It has slowed TransMid's testing and, worse, denied the
drug to patients not in trials.

Indeed, TransMid has taken so long that a much newer glioblastoma drug is
neck and neck in development. Made by NeoPharm, "IL13" is conceptually
similar to TransMid.

The only other glioblastoma innovation over the last 20 years has been
chemotherapy wafers that are implanted in the brain.

The upshot is that the prognosis for glioblastoma multiforme patients is
as grim today as it was 20 years ago. Most victims die within 12 to 15
months of diagnosis, many in their prime.

When TransMid's third and most important trial began in June 2004, the
goal was to sign up 323 patients. Today, there are just 104 patients at 56
sites worldwide.

It's not that patients are reluctant; they have so little hope, they're
eager to enroll. But hospitals have few eligible patients, and many of
them die before they get a chance to try TransMid. At Cooper, months after
Rossi's presentation there, just one patient is enrolled. A second is
about to join.

Enrollment criteria have been eased so more patients - those with larger
tumors, for instance - can get in.

http://www.xenova.co.uk/dc_transmid.html
Phase I and Phase II clinical trials for TransMIDTM have been
successfully completed in patients suffering from inoperable, recurrent
high grade gliomas who have failed to respond to all other forms of
treatment. A Phase I dose-escalating study was performed at the NIH in the
US and was followed by a Phase II multi-centre study at nine premier US
medical centres.

In the Phase II study, a reduction in tumour size of 50% or more was noted
in 35% of evaluable patients, with a corresponding increase in life
expectancy in those patients that did respond. In this study, median
survival for patients receiving TransMIDTM was approximately 37 weeks.
This compares to historical average life expectancy of approximately 26
weeks for patients with this condition, currently being treated with best
standard of care.

In May 2004 agreement was reached with the US Food and Drug Administration
(FDA) under the Special Protocol Assessment (SPA) procedure for the
revised Phase III clinical trial programme proposed for TransMID TM.

TransMIDTM received fast track status from the FDA in August 2001 and
orphan drug status in December 2001. In addition, the European Commission
granted TransMID TM orphan designation in March 2002 and in February 2005
obtained orphan drug designation in Japan .

TransMIDTM is currently licensed to Sosei in Japan, Nycomed in Europe,
Medison in Israel, Ranbaxy in India and PharmaEngine in China and South
Korea . The rights to TransMID TM in North America have been retained.
For further information:

http://www.gbmtrial.com

http://www.clinicaltrials.gov

http://www.cancerhelp.org.uk
_____________________________________________
So watch for results of the PHase III that just finished AND
it's probably small cohorts at each trial centre.
J

.