http://www.fda.gov/bbs/topics/news/2006/NEW01316.html

Press Release

New Federal Health
Initiative to Improve Cancer Therapy
Patients will Benefit from Rapid Development and
Delivery of New Cancer Treatments

The Food and Drug Administration (FDA), the National Cancer
Institute (NCI), part of the National Institutes of Health, and the
Centers for Medicare & Medicaid Services (CMS) today announced the
Oncology Biomarker Qualification Initiative (OBQI) — an agreement to
collaborate on improving the development of cancer therapies and the
outcomes for cancer patients through biomarker development and
evaluation.

Biomarkers are biologic indicators of disease or therapeutic
effects, which can be measured through dynamic imaging tests, as well
as tests on blood, tissue and other biologic samples. This initiative
is the first time these three Department of Health and Human Services
(HHS) agencies have focused together on biomarkers as a way of speeding
the development and evaluation of cancer therapies.

“We are excited about this effort to speed the development and
delivery of new cancer treatments for patients,” said Secretary of
Health and Human Services Mike Leavitt. “By bringing together the
scientific, regulatory and delivery expertise of these three agencies,
we can bring targeted, more personalized cancer diagnostics, treatments
and preventions to patients more rapidly.”

The collaboration will develop scientific understanding of how
biomarkers can be used to assess the impact of therapies and better
match therapies to patients. For instance, OBQI will address questions
such as how particular biomarkers can be used to:

• Assess after one or two treatments if a patient';s tumor is
  responding to treatment
• Determine more definitively if a tumor is dying, even if it is
  not shrinking
• Identify which cancer patients are at high risk of their tumor
  coming back after therapy
• Determine if a patient';s tumor is likely to respond at all to a
  specific treatment
• Efficiently evaluate whether an investigational therapy is
  effective for tumor treatment.

The goal of OBQI is to validate particular biomarkers so that they
can be used to evaluate new, promising technologies in a manner that
will shorten clinical trials, reduce the time and resources spent
during the drug development process, improve the linkage between drug
approval and drug coverage, and increase the safety and appropriateness
of drug choices for cancer patients.

“Almost four years ago, NIH set out to create a “roadmap” for 21st
century medical research. Programs like OBQI will be central to that
vision, not only because they will lead to vital discoveries about the
biology of disease, but because they will be models for scientific
collaboration,” said NIH Director Elias A. Zerhouni, M.D.

“An enhanced understanding of clinical biomarkers will help make the
development of diagnostics and treatments more targeted, one of our
most pressing goals under the Critical Path Initiative, FDA';s program
to modernize the medical product development process,” said FDA Acting
Commissioner of Food and Drugs Andrew C. von Eschenbach, M.D. “We
believe partnerships that help us standardize the use of new
technologies are essential to refining the drug development process, so
we can bring personalized medicines to patients more quickly and
ultimately improve outcomes.”

Under the OBQI, biomarker research will be focused in four key
areas: standardizing and evaluating imaging technologies to see in more
detail how treatments are working, developing scientific bases for
diagnostic assays to enable personalized treatments, instituting new
trial designs to utilize biomarkers, and pooling data to ensure that
key lessons are shared from one trial to another. By working with
academic and industry scientists, as well as professional
organizations, the OBQI teams can foster the development of key
information on biomarkers through clinical trials.

“By identifying biomarkers for specific cancers and clinically
evaluating them, researchers will have an evidence base for their use
in targeted drug development and to determine which therapies are
likely to work for patients before treatment selection,” said NCI
Deputy Director Anna D. Barker, Ph.D. “Rather than waiting weeks to
months to determine if a specific drug works for a patient, biomarkers
could be used to monitor real-time treatment responses.”

The first OBQI project to be implemented will serve to validate and
standardize the use of Fluorodeoxyglucose – Positron Emission
Tomography (FDG-PET) scanning. PET scans are used to characterize
biochemical changes in a cancer. Under the collaboration, researchers
will use FDG-PET imaging technology in trials of patients being treated
for non-Hodgkin';s lymphoma, to determine if FDG-PET is a predictor of
tumor response. Data resulting from this type of evidence-based study
will help both FDA and CMS work with drug developers based on a common
understanding of the roles of these types of assessments.

“There are many steps between a novel scientific idea with
tremendous promise and a new drug reliably benefiting patients,” said
CMS Administrator Mark B. McClellan, M.D., Ph.D. “This collaboration
will produce evidence that will help people with Medicare and Medicaid
get better care more quickly, as a result of better-targeted treatment
decisions for cancer patients.”

Over the next several months, the OBQI team will design a number of
initiatives to identify and clinically qualify other cancer biomarkers.
The new initiatives will bring together scientists from many sources
and address agency priorities identified through FDA';s Critical Path
and NIH';s Roadmap Initiatives. The OBQI also represents the work of
the NCI-FDA Interagency Oncology Task Force (IOTF). The IOTF is a
collaboration between NCI and FDA to enhance the efficiency of clinical
research and the scientific evaluation of new cancer treatments. The
two agencies, along with CMS, share knowledge and resources to
facilitate the development of new cancer drugs and diagnostics and
speed their delivery to patients as safely and as cost-effectively as
possible.

FDA Critical Path

Critical Path is the FDA';s premier initiative to identify and
prioritize the most pressing medical product development problems and
the greatest opportunities for rapid improvement in public health
benefits. Its primary purpose is to ensure that basic scientific
discoveries translate more rapidly into new and better medical
treatments by creating new tools to find answers about how the safety
and effectiveness of new medical products can be demonstrated in faster
timeframes with more certainty and at lower costs.

The NIH Roadmap

The NIH Roadmap is a series of new initiatives designed to pursue
major opportunities and gaps in biomedical research that no single NIH
institute could tackle alone, but which the agency as a whole can
address to make the biggest impact possible on the progress of medical
research, and to catalyze changes that will serve to transform new
scientific knowledge into tangible benefits for public health.
Additional information about the NIH Roadmap can be found at its Web
site, www.nihroadmap.nih.gov.

For information about the Food and Drug Administration, please visit
http://www.fda.gov.
For additional information about the National Cancer Institute, please
visit http://www.cancer.gov.
For information about the Centers for Medicare & Medicaid Services,
please visit http://cms.hhs.gov.

FDA/NCI/CMS
Memorandum of Understanding

###

Clinical Trial: Summary: Study of Gamma Knife Radio Surgery and Temozolomide for Patients with
1- 4 Unresected Brain Metastases

http://www.centerwatch.com/patient/studies/stu87321.html

Summary: Study of Gamma Knife Radio Surgery and Temozolomide for
Patients with 1- 4 Unresected Brain Metastases
The purpose of this study is to determine if Gamma Knife radiosurgery
with Temodar improves the overall survival time of patients with one to
four brain metastases (cancer to the brain). All patients will receive
stereotactic radiosurgery (Gamma Knife), done on a single day,
outpatient procedure and chemotherapy with temodar may be given up to
24 months, depending on your tumor response.

Patient Inclusion Criteria

Confirmed diagnosis of cancer with 1-4 brain metastases.
No previous cranial radiation.
No chemotherapy within one month prior to treatment.
No prior surgery for brain metastases.
No allergy to MRI contrast dye.
Age > 18.
Patient Exclusion Criteria

Diagnosis of lymphoma, small cell lung cancer and germ cell tumor.
Systemic therapy within 1 month prior to treatment.
Major medical illnesses or psychiatric impairments, which in the
investigator's opinion will prevent administration of completion of the
protocol therapy and/or interfere with follow-up.
All patients who have undergone a complete resection of all known brain
metastases.

Contact:

Laszlo Mechtler, MD
Roswell Park Cancer Institute
Elm & Carlton Streets
Buffalo, NY 14263
Telephone: 716-845-3154
Email: Laszlo.mechtler@roswellpark.org 

This site is run by CenterWatch, a publishing company that focuses on
the clinical trials industry. The information provided in this service
is designed to help patients find clinical trials that may be of
interest to them, and to help patients contact the centers conducting
the research. CenterWatch is neither promoting this research nor
involved in conducting any of these trials.

Trial listings updated: February 17, 2006 at 3:52:01 PM

Radiolabeled Monoclonal Antibody Therapy in Treating Patients
With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

http://www.clinicaltrials.gov/ct/show/NCT00089245?order=100

This study is currently recruiting patients.
Verified by National Cancer Institute (NCI) August 2004
Sponsors and Collaborators: Memorial Sloan-Kettering Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089245

Purpose

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells
and deliver tumor-killing substances, such as radioactive iodine, to
them without harming normal cells.

PURPOSE: This phase I trial is studying the side effects and best dose
of radiolabeled monoclonal antibody therapy in treating patients with
refractory, recurrent, or advanced CNS or leptomeningeal cancer.

Condition                                                                            
Intervention                                                    Phase
Adult Brain
Tumor                                                                
Drug: iodine I 131 monoclonal antibody 8H9     Phase I
Adult
Medulloblastoma                                                         
Procedure: antibody therapy
Adult Rhabdomyosarcoma                                               
     Procedure: biological response modifier therapy
Adult Soft Tissue
Sarcoma                                                     Procedure:
isotope therapy
Childhood
Medulloblastoma                                                  
Procedure: monoclonal antibody therapy
Childhood Rhabdoid Tumor of the Central Nervous System    Procedure:
radiation therapy
Childhood Rhabdomyosarcoma                                             
Procedure: radioimmunotherapy
Childhood Soft Tissue Sarcoma
Desmoplastic Small Round-Cell Tumor
Disseminated Neuroblastoma
Leptomeningeal Metastases
Metastatic Childhood Soft Tissue Sarcoma
Metastatic Osteosarcoma
Metastatic Tumors of the Ewing's Family
Neuroblastoma
Osteosarcoma
Previously Treated Childhood Rhabdomyosarcoma
Tumors of the Ewing's Family

MedlinePlus related topics: Bone Cancer; Brain Cancer; Cancer; Cancer
Alternative Therapies; Neuroblastoma;   Neurologic Diseases; Soft
Tissue Sarcoma
Genetics Home Reference related topics: Cancer; Neurologic Diseases

Study Type: Interventional
Study Design: Treatment

Official Title: Phase I Study of Intrathecal Iodine I 131 Monoclonal
Antibody 8H9 in Patients With Refractory, Recurrent, or Advanced CNS or
Leptomeningeal Cancer

Further study details as provided by National Cancer Institute (NCI):

OBJECTIVES:

   * Determine the maximum tolerated dose of intrathecal iodine I 131
monoclonal antibody 8H9 in patients with refractory,
        recurrent, or advanced CNS or leptomeningeal cancer.
   * Determine the clinical toxic effects of this drug in these
patients.
   * Determine the pharmacokinetics and dosimetry of this drug in these
patients.
   * Correlate tumor response by MRI with CSF reverse-transcription
polymerase chain reaction in patients treated with
        this drug.

OUTLINE: This is a dose-escalation study.

Patients receive iodine I 131 monoclonal antibody 8H9 (^131I MOAB 8H9)
intrathecally on day 1. Treatment repeats every 4 weeks for up to 2
courses (total of 2 injections) in the absence of disease progression
or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ^131I MOAB 8H9
until the maximum tolerated dose (MTD) is determined. The MTD is
defined as the dose preceding that at which 2 of 3 or 2 of 6 patients
experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this
study within 2-3 years.

Eligibility
Genders Eligible for Study: Both
Criteria

DISEASE CHARACTERISTICS:

   * Histologically confirmed CNS or leptomeningeal cancer, meeting 1
of the following criteria:
   * Refractory to conventional therapy OR for which no conventional
therapy exists
   * Less than 10% chance of cure with conventional therapy
   * Recurrent brain tumor or other solid tumor with a predilection for
leptomeningeal dissemination, including, but not
        limited to, the following:
   * Medulloblastoma
   * Ewing's sarcoma/primitive neuroectodermal tumor
   * Rhabdoid tumor
   * Neuroblastoma
   * Osteosarcoma
   * Desmoplastic small rounded-cell tumor
   * Rhabdomyosarcoma
   * 8H9 reactivity confirmed by immunohistochemical staining
   * No rapidly progressing or deteriorating neurologic examination
   * Stable neurological deficits as a result of brain tumor allowed
   * No obstructive or symptomatic communicating hydrocephalus

PATIENT CHARACTERISTICS:

Age
    * Any age

Performance status
    * Not specified

Life expectancy
    * Not specified

Hematopoietic
    * Absolute neutrophil count > 1,000/mm^3
    * Platelet count > 50,000/mm^3

Hepatic
    * No hepatic toxicity ≥ grade 2

Renal
    * No renal toxicity ≥ grade 2

Cardiovascular
    * No cardiac toxicity ≥ grade 2

Pulmonary
    * No pulmonary toxicity ≥ grade 2

Other
    * Not pregnant or nursing
    * Negative pregnancy test
    * Concurrent active malignancy outside the CNS allowed
    * No uncontrolled life-threatening infection
    * No gastrointestinal system toxicity ≥ grade 2
    * No other severe major organ toxicity
    * Hearing loss ≤ grade 3

PRIOR CONCURRENT THERAPY:

Biologic therapy
    * Not specified

Chemotherapy
    * At least 3 weeks since prior systemic chemotherapy

Endocrine therapy
    * Prior corticosteroids allowed

Radiotherapy
    * At least 3 weeks since prior cranial or spinal radiotherapy

Surgery
    * Not specified

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier  NCT00089245

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York, 
10021,  United States; Recruiting
      Clinical Trials Office for Memorial Sloan-Kettering Cancer Cen 
646-227-2149

Study chairs or principal investigators
      Kim Kramer, MD,  Study Chair,  Memorial Sloan-Kettering Cancer
Center  

More Information

Clinical trial summary from the National Cancer Institute's PDQ®
database
Study ID Numbers:  CDR0000378183; MSKCC-03133
Last Updated:  February 7, 2006
Record first received:  August 4, 2004
ClinicalTrials.gov Identifier:  NCT00089245
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2006-02-21

Int J Clin Oncol. 2005 Dec;10(6):438-40.

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16369750&dopt=Abstract

A new therapeutic approach in patients with advanced sarcoma.

Kasper B, Ho AD, Egerer G.

University of Heidelberg, Department of Internal Medicine V, Im
Neuenheimer Feld 410, D-69120 Heidelberg, Germany.
Bernd.Kasper@med.uni-heidelberg.de

Sarcomas represent a rare and heterogeneous disease and the prognosis
of patients remains poor, with a disease-free survival at 5 years of
less than 10%. Only a few chemotherapeutic agents, such as doxorubicin
and ifosfamide, have been identified to be active with response rates
above 20%. The concept of angiostatic therapy in combination with
proapoptotic biomodulators and chemotherapeutics has not been evaluated
in these patients. Therefore, the efficacy of low-dose trofosfamide in
combination with the peroxisome proliferator-activated
receptor-gamma-agonist, pioglitazone, and the selective
cyclooxygenase-2 inhibitor, rofecoxib, was evaluated in a pilot study.
Six patients with advanced sarcoma received a combination of oral
pioglitazone plus rofecoxib and, after 14 days, oral trofosfamide. The
therapy was administered continuously daily. Four patients received the
triple combination as maintenance therapy; three of them achieved
stabilization of disease. Two patients received the combination as
relapse therapy; however, it failed to stop disease progression. Side
effects were generally mild and hospitalization was not necessary. This
new triple combination of low-dose trofosfamide, pioglitazone, and
rofecoxib may represent a feasible new alternative in the palliative
treatment of sarcoma patients.

PMID: 16369750 [PubMed – in process]