IBTA e-News – January 2012

By 16th January 2012e-News Archive

Dear Friend,

Patient resource: There is a very useful podcast explaining a CT scan to patients that was released on 2 January by ASCO. It is available here and lasts for 5 mins 40 secs. While intending to cover all cancers it answers most questions asked by a patient referred for a CT scan of the brain.

Paediatric brain tumour research: In a recent report US Phrma identified 53 medicines in clinical trial development or FDA review for paediatric cancer of which 12 were specifically associated with brain tumours, while several others were being investigated for solid tumours in general.

The name, indication  and status of the brain tumour medicines or therapies are:  ARC-100 (medulloblastoma) Phase I/II; cintredekin besodotox  (glioma) Phase I; GliAtak (malignant brain tumors), Phase I; Nexavar (glioma), Phase II; nimotuzumab (recurrent glioma), Phase II; PTC299 (CNS cancer) Phase 1; SL-701 (glioma) Phase I/II; Tarceva (recurrent/refractory ependymoma) Phase II; TheraCIM (recurrent DIPG) Phase II; vismodegib (medulloblastoma) Phase II;  Xeloda (gliomas) Phase I; Xerecept (brain edema associated with brain tumors) Phase I/II.

Those therapies listed above appear to be company-initiated studies, as opposed to investigator-initiated studies. For example, the CERN Foundation also has an on-going paediatric study  (CERN08-01) of bevacizumab and Lapatinib for recurrent or refractory ependymoma.

MRS and IDH1: Scientists have used magnetic resonance spectroscopy (MRS) to identify the IDH1 mutation in both tumour samples and patients with glioma brain tumours by searching for the molecule 2-hydroxyglutarate (2HG). It has been suggested that this may "dispense with the need for invasive surgery". Hopefully, the results of this technique will be used to develop targeted therapies, rather than just tracking a patient's progress.

At the present  time surgery is used not only to identify the type and grade of tumour but as a debulking process prior to use of the concomitant therapy.  Patients are likely to be puzzled should a Doctor say: "We don't need to operate, from the MRS we know you have a glioma with the IDH1 mutation".  In a recently released US Patterns of Care (POC) study for 2006 approximately 65% of patients with a GBM received a partial or total resection. There might be a relevance for the MRS technique in the case of inoperable tumours.

Drug shortages: The USA has continued to experience shortages of drugs, particularly sterile injectable drugs, including those relevant to cancer treatments.  It is not known if this has had a flow-on effect in other countries. Drugs currently on the FDA's  shortage list, which shows individual supplier shortages and alternative sources, and which may be relevant to brain tumour treatments, include: Cisplatin injection 1 mg/mL solution,  Dexamethasone Injection, Methotrexate Injection-Preservative Free, Midazolam Injection,  Ondansetron Injection 2 mg/mL, Vincristine Sulfate Injection.

Commemoration and conference days: 7 February has been designated as International Childhood Cancer  Awareness Day. Now that CNS tumours have overtaken all leukaemias as the greatest childhood cancer killer in many countries it represents an opportunity to raise awareness about the need for greater support and research for paediatric brain tumours.

Rare Disease Day will be marked in Europe on 29 February - chosen because that date is a "rare date".  In the USA on 29 February the National Institutes of Health will also hold a Rare Disease Day. On the following day (1 March) the FDA will host a Rare Disease Patient Advocacy Day. By definition all paediatric cancers are "rare diseases".  In Brussels on 10 February the European Society for Medical Oncology (ESMO) and Rare Cancers Europe (RCE)  will jointly sponsor a conference on clinical trial methodology for rare cancers.

Trabedersen: On 11 January  Antisense Pharma  announced  that  they have decided to terminate  the ongoing Phase III trial (the Sapphire trial) for recurrent or refractory anaplastic astrocytoma (AA) or secondary glioblastoma (GBM ) due to slow patient recruitment. The company will pursue 1st line treatment of GBM with standard of care.  We will advise when any information about the next  trial in high grade glioma is available.

The company stated: " Recruitment delays are a result of changes in the histopathological grading of patients, introduced by the WHO, which considerably reduced the number of patients diagnosed with AA, already a rare, orphan disease. In addition, advances in the standard of care for 1st line patients have rendered many treated patients unsuitable for inclusion, as they no longer receive radiotherapy. Attempts by the management to identify and implement an effective solution, such as amendments to the study design, have not yielded significant improvements in the recruitment rate."

Recent developments and promising therapies: Two researchers from Barcelona have discovered that the molecule CPEB4 turns on hundreds of genes that play critical roles in the progression  of pancreatic cancer and brain tumours. Inhibiting the process might be a useful form of targeted therapy.

Dutch company to-BBB has received a grant of €600,000 from a Dutch government agency to support a brain drug delivery partnership with a (as yet unnamed) top-5 pharma company using its G-Technology which enhances the delivery of specific drugs to the brain. In June 2011 the Company announced approval for a Phase I/II clinical trial testing its product  2B3-101 for brain metastases from breast cancer.

Northwest Biotherapeutics: On 9 January the company announced plans to have at least 30 sites open and enrolling by the first quarter of 2012 for its DCVax immune therapy for GBM and will pursue programs in Europe.

On 4 January Celldex Therapeutics announced "...  that patient screening has initiated in a Phase 2 trial of rindopepimut in combination with Avastin in patients with recurrent epidermal growth factor variant III (EGFRvIII)-positive glioblastoma, called the “ReACT Study.” This new study will run in parallel with Celldex’s Phase 3 trial (ACT IV) evaluating rindopepimut in patients with newly diagnosed EGFRvIII-expressing glioblastoma (GB)."

On 5 January the German-based company Apogenix announced the raising of further funds to advance the Phase II clinical trial of its drug APG101 to treat GBM. Final results of the trial are expected in the first quarter of this year. One of the investors is the German Cancer Research Centre.

Brain tumours and weather forecasting: The complete novelty of a scientific paper which seeks  to apply principles of weather forecasting to the spread of an individual's GBM was bound to attract attention in the popular media. The open-access paper can be downloaded here. In a subsequent interview the principal author Eric Kostelich from the University of Arizona revealed that he was prompted to focus on brain tumours because he had a family member with a brain tumour.

The authors believe that  "... this preliminary study demonstrates the potential feasibility of ensemble forecasting and data assimilation methods for short-term prediction of the growth and spread of malignant brain tumors." They warn that "considerable work remains before our approach can be seriously considered in clinical settings." In the interview referred to earlier Kostelich suggests that the research (essentially based on MRIs and the behaviour of GBMs in other patients) might enable pre-emptive action to forestall development of a GBM in a certain direction, or a forecast that continuation of a chemotherapy might be unproductive.

In all such research the evaluative criteria should be "will this be of benefit to the patient", rather than simply helping the clinician to confirm the accuracy of a rather dire prognosis.

Danish brain tumour statistics: The 2010 report of the Danish Cancer Registry notes an increased incidence of CNS tumours in men. In the rather uncertain language of a Google translation it is stated: "There was a significant increase of tumors in the brain and central nervous system in men. The increase is 16 percent. in incidence rate, the responses to (which corresponds to?) an increase in the number from 638 to 748 (between 2009 and 2010?). There is no similar increase among women. The reason for the increase in men is uncertain. Over the past 10-year period (we have) seen a steady increase, which to some extent (is) a reflection of increased diagnosis as a result of a general focus on the detection of cancer with highly increased imaging activity."

IBTA Co-Director Kathy Oliver will attend the Drug Information Association  conference in Copenhagen in March and in April it is hoped that IBTA officials can meet with representatives of the Scandinavian brain tumour support and advocacy groups to discuss areas of common interest.

2012 IBTA Brain Tumour magazine:  Work has commenced on the 2012 edition of the IBTA's Brain Tumour magazine.  The suggestions about content made by 279 respondents to the IBTA's 2011 satisfaction survey have been carefully analysed and incorporated where possible in the magazine planning. Two recommended subjects we would like to cover and for which we are seeking authors are: (1) the relevance of stereotactic radio surgery for meningiomas, and (2) the use of boswellia in Germany for brain oedema as an example of a useful complementary treatment.  Please contact chair@theibta.org if you know of possible contributors on these subjects.  Limited copies of the 2011 Brain Tumour  magazine are still available and free copies can be requested here.

Thank you for your continuing support. We wish all our readers a successful New Year.

Denis Strangman(Chair and Co-Director)
International Brain Tumour Alliance IBTA
www.theibta.org

Kathy Oliver (Co-Director)
PO Box 244, Tadworth, Surrey
KT20 5WQ, United Kingdom
Tel:+ (44) + (0) + 1737 813872
Fax: + (44) + (0) +1737 812712
Mob: + (44) + (0) + 777 571 2569

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