Original Article

Bone Marrow Transplantation advance online
publication 4 February 2008; doi: 10.1038/bmt.2008.2

Myeloablative therapy with autologous stem cell rescue for
patients with Ewing sarcoma

S L Gardner¹, J Carreras², C Boudreau³, B M Camitta⁴, R H Adams⁵, A R Chen⁶, S M Davies⁷, J R Edwards⁸, A C Grovas⁹, G A Hale¹⁰, H M Lazarus¹¹, M Arora¹², P J Stiff¹³ and M Eapen²

1. ¹Department of Pediatric Oncology, New York
   University, New York, NY, USA
2. ²Statistical
   Center, Center for International Blood and Marrow Transplant Research,
   Medical College of Wisconsin, Milwaukee, WI, USA
3. ³Department of Statistics & Actuarial
   Science, University of Waterloo, Waterloo, Ontario, Canada
4. ⁴Department of Pediatrics, Medical College
   of Wisconsin, Milwaukee, WI, USA
5. ⁵BMT Internal Medicine, Mayo Clinic Arizona,
   Phoenix, AZ, USA
6. ⁶Department of Pediatric Oncology, John
   Hopkins Hospital, Baltimore, MD, USA
7. ⁷Department of Bone Marrow Transplantation,
   Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA
8. ⁸Department of Bone Marrow Transplantation,
   Florida Hospital Cancer Institute, Orlando, FL, USA
9. ⁹Department of Pediatrics, University of
   Nebraska Medical Center, Omaha, NE, USA
10. ¹⁰Department of Bone Marrow
    Transplantation, St Jude Children's Research Hospital, Memphis, TN, USA
11. ¹¹Department of Hematology/Oncology,
    University Hospitals of Cleveland, Cleveland, OH, USA
12. ¹²Department of Hematology/Oncology,
    University of Minnesota, Minneapolis, MN, USA
13. ¹³Department of Bone Marrow
    Transplantation, Loyola University Medical Center, Maywood, IL, USA

Correspondence:
Dr M Eapen, Statistical Center, Center for International Blood and
Marrow Transplant Research, Medical College of Wisconsin, 8701
Watertown Plank Road, Milwaukee, WI 53226, USA. E-mail: meapen@mcw.edu

Received 20 August 2007; Revised 19 December 2007;
Accepted 20 December 2007; Published online 4 February 2008.

The aim of this study was to identify risk factors
associated with PFS in patients with Ewing sarcoma undergoing ASCT; 116
patients underwent ASCT in 1989–2000 and reported to the Center for
International Blood and Marrow Transplant Research. Eighty patients
(69%) received ASCT as first-line therapy and 36 (31%), for recurrent
disease. Risk factors affecting ASCT were analyzed with use of the Cox
regression method. Metastatic disease at diagnosis, recurrence prior to
ASCT and performance score <90 were associated with higher rates of
disease recurrence/progression. Five-year probabilities of PFS in
patients with localized and metastatic disease at diagnosis who
received ASCT as first-line therapy were 49% (95% CI 30–69) and 34%
(95% CI 22–47) respectively. The 5-year probability of PFS in patients
with localized disease at diagnosis, and received ASCT after recurrence
was 14% (95% CI 3–30). PFS rates after ASCT are comparable to published
rates in patients with similar disease characteristics treated with
conventional chemotherapy, surgery and irradiation suggesting a limited
role for ASCT in these patients. Therefore, ASCT if considered should
be for high-risk patients in the setting of carefully controlled
clinical trials.

http://www.ncri.org.uk/ncriconference/info/releases/pr5.pdf

Early Stage Drug Shows Promise
Against Cancer Cells from Young Patients

A NEW drug has shown promising pre-clinical activity
against cells from several types of children’s cancers,
scientists reveal at the National Cancer Research
Institute Conference in Birmingham today (Tuesday).
http://www.ncri.org.uk/ncriconference
Scientists from Cancer Research UK’s Paterson
Institute at the University of Manchester have shown
in laboratory tests that the drug RH1 can kill tumour
cells from neuroblastoma, osteosarcoma and Ewing’s
sarcoma, three types of childhood and adolescent cancer
that are often resistant to current types of chemotherapy.
Despite increases in survival rates for childhood cancers,
new drugs are needed to combat drug resistance seen in
current treatments. On the strength of these pre-clinical
results, the researchers are planning a phase 1 trial for
the drug involving children with cancer.
All cells have natural suicide mechanisms that become
active when cells are damaged or grow uncontrollably.
In cancer cells, this suicide mechanism switches off or
becomes faulty and treatment is needed to encourage
the process.
The researchers – based at the Paterson Institute for
Cancer Research Manchester ( http://www.mcrc.manchester.ac.uk
) and the Royal Manchester
Children’s Hospital ( http://www.cmmc.nhs.uk
) – found in their pre-clinical study
that even very low doses of RH1 could increase cancer
cell death by around 50 per cent when compared with
untreated cells.
RH1’s activity is greatly enhanced by an enzyme, DTdiaphorase
(DTD), which is found in higher quantities
in many adult tumours, including lung, liver and breast
cancers, and the drug has recently completed phase 1
studies in adults.
Dr Guy Makin, the study’s lead researcher from the
Paterson Institute ( http://www.paterson.man.ac.uk
) said: “We are very excited that we
have been able to work with a new drug that has only
just completed an adult phase 1 study. RH1 is a very
potent agent and our pre-clinical results suggest that
it could be effective against childhood tumours that
express DTD. We hope that this will be just the first
of many new agents that we can show are useful for
treating childhood cancer.”
The planned trial would be the first for a drug tested
for children through Cancer Research UK’s drug
development office.
Dr Bruce Morland, chairman of the Children’s Cancer and
Leukaemia Group (CCLG, http://www.ukccsg.org
), who were instrumental in the
selection of RH1 for evaluation, said: “Survival rates for
children with cancer are already high at 75 per cent. But
in many cases, patients become resistant to their drugs
and need new options.
“This is an exciting moment in the history of the CCLG.
Our increasingly close relationship with the Cancer
Research UK drug development office means new
potentially promising anticancer drugs can be tested in
children at a much earlier point in their development.
In this way we hope that new, effective drugs are
introduced in the fight against children’s cancer at
the earliest opportunity, saving even more lives in the
process.”
RH1 was synthesised from MeDZQ, an anti-tumour
chemical that selectively kills cancer cells. The RH1
compound was manufactured by scientists to be a watersoluble
version of MeDZQ, making it more effective as a
drug for potential clinical use.
Dr Sally Burtles, Cancer Research UK’s ( http://www.cancerresearchuk.org
) director of drug
development, said: “Helping more children survive
cancer by finding new treatments is a top priority for
the charity. Currently, not many drugs are developed
specifically for children so it’s great news that the drug is
showing such encouraging effects in preclinical studies.
We hope this type of drug development will continue
and help improve the treatment of childhood cancer
patients.”

How to contact the Manchester Cancer Research Centre:
Manchester Cancer Research Centre
The University of Manchester
Wilmslow Road
Withington
Manchester
M20 4BX
England
Tel: +44 0161 446 3156 (From the USA, 011-44-161-446-3156)
Fax: +44 0161 446 3109
email mcrc@manchester.ac.uk

Central Manchester and Manchester Children's University Hospitals NHS
Trust
Trust Headquarters, Cobbett House
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
Tel: +44 (0)161 276 1234 (From the USA, 011-44-161-276-1234
Fax: +44 (0)161 273 6211 (Trust HQ)

http://www.rocheusa.com/newsroom/current/2007/pr2007102302.html

October 23, 2007 — Nutley N.J.
 
Roche Announces Positive Results in Solid Tumors Using Human Monoclonal
Antibody against IGF-1R (R1507)
 
Today, Roche announced positive results from a Phase I trial of R1507,
a human monoclonal antibody to target IGF-1R (insulin-like growth
factor receptor), in patients with solid tumors. IGF-1 is one of the
most potent natural activators of the AKT and MAPK signaling pathways,
which promote cell growth and cell survival. The IGF-1R pathway has
also been shown to have an important role in mediating the resistance
to cytotoxic drugs and EGFR/HER2-targeted agents. The results were
reported during the AACR-NCI-EORTC International Conference on
Molecular Targets and Cancer Therapeutics, held in San Francisco.

Study Results
In the Phase I study, R1507 was administered by intravenous infusion.
Nine of 34 adult patients with advanced solid tumors experienced
disease stabilization. Four of the seven heavily pretreated patients
with Ewing’s sarcoma demonstrated clinical benefit with two of these
patients achieving durable, objective partial responses.

Once a week administration of R1507 was well tolerated with very few
side effects. Treatment with R1507 was not associated with the typical
side-effects normally observed with cancer therapy (e.g., low blood
counts, infection, hair loss, severe nausea and vomiting).  The most
frequent side effects observed were fatigue, anorexia and weight loss,
symptoms that are commonly observed in patients with advanced cancer.

 “We are very encouraged by these early results with R1507 in patients
with refractory Ewing’s sarcoma,” said Kapil Dhingra, MD, Head,
Oncology Disease Biology Area at Roche. “As a result, we have given
this program a very high priority as we believe this molecule has the
potential to be very beneficial in treating patients with sarcoma as
well as a variety of other solid tumors.”

The antibody (R1507) was initially developed under Roche’s broad
antibody development collaboration with Genmab, which began in 2001.

The Phase I study is being conducted at four sites in the U.S.,
including the University of Colorado Cancer Center (Aurora, CO), The
University of Texas M.D. Anderson Cancer Center (Houston, TX), Cancer
Institute of New Jersey (New Brunswick, NJ) and The Institute for Drug
Development (San Antonio, TX).  R1507 has also been investigated in 26
patients on a three week schedule in the Phase I study.  This treatment
schedule was also generally well tolerated with a side effect profile
similar to the weekly schedule.

“This drug attacks the IGF pathway and may provide a new class of drugs
to treat a variety of cancers, including breast, prostate, colon,
melanoma, myeloma and a variety of sarcomas, which could greatly add to
the way that we currently treat these patients,” says Stephen Leong,
M.D., assistant professor of Medical Oncology at the University of
Colorado Cancer Center and lead author of the abstract.

Razelle Kurzrock, MD,  investigator at the M.D. Anderson Cancer Center
and the senior author of the abstract, noted that some of the responses
were very impressive.  For instance, one 28 year-old Ewing’s sarcoma
patient with large tumors unresponsive to many other treatments showed
dramatic tumor shrinkage within six weeks, without side effects.  “This
is one of the best responses I've seen in over 20 years of oncology
experience,” stated Dr. Kurzrock.  

Based on these initial results with R1507, Roche plans to conduct
additional trials and work with a global consortium of sarcoma experts,
including the Sarcoma Alliance for Research through Collaboration
(SARC). “We are very excited about our collaboration with SARC, which
represents a new approach to sarcoma clinical trials, and we look
forward to combining our expertise with that our colleagues at SARC to
expedite new sarcoma treatments,” added Dhingra.

“We are excited to be partnering with Roche on the development of a new
treatment against an important target, which could result in a
potential breakthrough treatment for sarcoma as well as other cancers,”
said Laurence Baker, DO, professor of Medicine and Pharmacology at the
University of Michigan and the Executive Director, SARC. “With Roche’s
considerable expertise in oncology and SARC’s vast network of
physicians and institutions, we look forward to determining the
potential of R1507 in this important disease area.”

About Ewing’s Sarcoma
The Ewing’s family of tumors (EFT) includes primary tumors of bone
(classic Ewing’s sarcoma, primitive neuroectodermal tumor, and Askin
tumor) and extraosseous primary tumors {National Cancer Institute}.
Studies using immunohistochemical markers, cytogenetics, molecular
genetics, and tissue culture indicate that these tumors are all derived
from the same primordial stem cell. EFTs account for 4 percent of
childhood and adolescent malignancies.  The estimated incidence (US) is
approximately 300 new cases per year. The median age for patients with
EFT is 15 years and more than 50 percent of patients are adolescents.
There is a slight male predominance and the lower limbs are affected in
40 percent of the patients.

Approximately 20 to 30 percent of the patients with ETB have overt
metastases at the time of diagnosis. However, outcomes for patients
with metastatic disease have improved little during the last 20 years.
Approximately 25-30 percent survival could be achieved with current
therapies for patients who present with metastatic disease at initial
diagnosis.

About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S.
pharmaceuticals headquarters of the Roche Group, one of the world’s
leading research-oriented healthcare groups with core businesses in
pharmaceuticals and diagnostics. For more than 100 years in the U.S.,
Roche has been committed to developing innovative products and services
that address prevention, diagnosis and treatment of diseases, thus
enhancing people's health and quality of life. An employer of choice,
in 2007 Roche was named Top Company of the Year by Med Ad News and one
of the Top 20 Employers (Science magazine). In 2006, Roche was ranked
the    No. 1 Company to Sell For (Selling Power), and one of AARP’s Top
Companies for Older Workers, and in 2005, Roche was named one of
Fortune magazine’s Best Companies to Work For in America. For
additional information about the U.S. pharmaceuticals business, visit
our websites: http://www.rocheusa.com
or www.roche.us.

About SARC
The purpose of the Sarcoma Alliance for Research through Collaboration
(SARC) is to engage all appropriate and necessary resources to cure and
prevent sarcoma.  SARC brings together expert sarcoma researchers and
clinicians from 29 centers of excellence in the United States.  SARC by
the charter, promotes international collaboration in sarcoma clinical
trials through is association with European sarcoma experts.  SARC is
unique as a clinical trial organization in that its trials at the
inception include pediatric and medical patients with sarcoma, because
sarcomas affect people of all ages.  SARC is a 501c3, non-profit
organization that is  headquartered in Ann Arbor, Michigan.

###
Contacts:     973-562-2699

Oncolytics Biotech Inc. Commences
Patient Enrolment in U.S. Phase II Sarcoma Clinical Trial

http://www.integratir.com/newsrelease.asp?news=2130983233&ticker=T.ONC&lang=EN&ny=on

6/27/2007 2:00:00 AM ET

CALGARY, AB, — June 27, 2007 –
Oncolytics Biotech
Inc. (“Oncolytics”) (TSX:ONC, NASDAQ:ONCY) announced today that patient
enrolment has commenced in its U.S. Phase II trial to evaluate the intravenous
administration of
REOLYSIN®
in patients with various sarcomas that have metastasized to the lung. Patients
are being enrolled at the Montefiore Medical Center/Albert Einstein College of
Medicine in the Bronx, New York, the University of Michigan Comprehensive Cancer
Center in Ann Arbor, and the Cancer Therapy and Research Center, Institute for
Drug Development in San Antonio, Texas.

“The initiation of this trial represents an important milestone for the
Company,” said Dr. Brad Thompson, President and CEO of Oncolytics. “We are now
treating patients with advanced cancers in Phase II clinical trials in the U.S.
and the U.K., with additional Phase II trials expected to begin before the end
of the year. These trials are expected to yield information that will guide the
late stage clinical development program for REOLYSIN®.”

The trial (REO 014) is a Phase II, open-label, single agent study whose primary
objective is to measure tumour responses and duration of response, and to
describe any evidence of antitumour activity of intravenous, multiple dose
REOLYSIN® in patients with bone and soft tissue sarcomas metastatic to the lung.
REOLYSIN® will be given intravenously to patients at a dose of 3×10(10) TCID(50)
for five consecutive days. Patients may receive additional five-day cycles of
therapy every four weeks for a maximum of eight cycles. Up to 52 patients will
be enrolled in the study.

Eligible patients must have a bone or soft tissue sarcoma metastatic to the lung
deemed by their physician to be unresponsive to or untreatable by standard
therapies. These include patients with osteosarcoma, Ewing sarcoma family
tumours, malignant fibrous histiocytoma, synovial sarcoma, fibrosarcoma and
leiomyosarcoma.

“There are very few treatment options for patients with bone or soft tissue
sarcomas,” said Dr. Matt Coffey, Oncolytics’ Chief Scientific Officer. “Our
decision to choose this indication is based on the observed activity of REOLYSIN®
against sarcomas in both preclinical and clinical studies.”

About Oncolytics Biotech Inc.
Oncolytics is a Calgary-based biotechnology company focused on the development
of oncolytic viruses as potential cancer therapeutics. Oncolytics’ clinical
program includes a variety of Phase I and Phase II human trials using REOLYSIN®,
its proprietary formulation of the human reovirus, alone and in combination with
radiation or chemotherapy. For further information about Oncolytics, please
visit www.oncolyticsbiotech.com

This press release contains forward-looking statements, within the meaning of
Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking
statements, including the Company’s expectations related to the U.S. Phase II
sarcoma clinical trial and the Company’s belief as to the potential of REOLYSIN®
as a cancer therapeutic, involve known and unknown risks and uncertainties,
which could cause the Company’s actual results to differ materially from those
in the forward-looking statements. Such risks and uncertainties include, among
others, the availability of funds and resources to pursue research and
development projects, the efficacy of REOLYSIN® as a cancer treatment, the
tolerability of REOLYSIN® outside a controlled test, the success and timely
completion of clinical studies and trials, the Company’s ability to successfully
commercialize REOLYSIN®, uncertainties related to the research and development
of pharmaceuticals and uncertainties related to the regulatory process.
Investors should consult the Company’s quarterly and annual filings with the
Canadian and U.S. securities commissions for additional information on risks and
uncertainties relating to the forward-looking statements. Investors are
cautioned against placing undue reliance on forward-looking statements. The
Company does not undertake to update these forward-looking statements.

FOR FURTHER INFORMATION PLEASE CONTACT:
Oncolytics Biotech Inc.
Cathy Ward
210, 1167 Kensington Cr NW
Calgary, Alberta T2N 1X7
Tel: 403.670.7377
Fax: 403.283.0858
cathy.ward@oncolytics.ca

The Equicom Group
Nick Hurst
325, 300 5th Ave. SW
Calgary, AB, T2P 3C4
Tel: 403.538.4845
Fax: 403.237.6916
nhurst@equicomgroup.com

The Investor Relations Group
Erika Moran
11 Stone St, 3rd Floor
New York, NY 10004
Tel: 212.825.3210
Fax: 212.825.3229
emoran@investorrelationsgroup.com

Hyperthermia Plus Chemotherapy Nearly Doubles Disease-Free Survival
Compared to Chemotherapy Alone for Sarcoma Cancer Patients

SALT LAKE CITY—June 4, 2007— BSD
Medical Corp. (AMX:BSM) announced
today that the results of a 340 patient randomized Phase III clinical
trial testing the benefit of adding hyperthermia therapy to
chemotherapy were presented at the annual American Society of Clinical
Oncology (ASCO) conference underway in Chicago, Illinois. According to
the results of this clinical study, which was conducted at nine major
European cancer treatment institutions and at Duke University Medical
Center in the USA, both disease-free survival time and local
progression free survival time for patients with locally advanced,
high-grade soft tissue sarcomas nearly doubled when hyperthermia
therapy was added to chemotherapy, as compared to patients who received
chemotherapy alone.

The patients enrolled in this clinical study were very ill, with
high-grade (II/III) soft tissue sarcomas and were at significant risk
of local failure and metastasis. The patients were randomly assigned to
receive either chemotherapy alone or chemotherapy combined with
hyperthermia therapy. The patient characteristics were well balanced
between these two groups. Their treatments were administered in 4
cycles every 3 weeks before and after surgery and radiation therapy.
For patients who received both hyperthermia therapy and chemotherapy
the median disease free survival was 31.7 months, compared to 16.2
months for those who received chemotherapy alone (p=0.004), a 95%
increase. The median local progression free survival rate was estimated
at 45.3 months for patients who received chemotherapy plus hyperthermia
therapy, compared to 23.7 months for patients who received chemotherapy
alone (p=0.01), a 91% increase.

The study was conducted under the direction of the European Society of
Hyperthermic Oncology (ESHO RHT-95) and the European Organization for
Research and Treatment of Cancer (EORTC 62961). Rolf Issels, MD PhD of
the Munich University Medical School in Germany, was the principal
investigator. Duke University was a participant in the international
study listed on the National Cancer Institute's website at
http://www.cancer.gov/clinicaltrials/EORTC-62961 under the NCI number
NCT00003052.

All hyperthermia treatments performed in the study were conducted
using
BSD-2000 hyperthermia systems developed and produced by BSD Medical
Corp. The BSD-2000 hyperthermia therapy system non-invasively delivers
precision focused hyperthermia therapy to cancerous tumors, including
tumors located deep in the body. The BSD-2000 is a recipient of the
Frost and Sullivan Technology Innovation of the Year Award for cancer
therapy devices.

About BSD Medical

BSD Medical Corp. is the leading developer of systems used to deliver
hyperthermia therapy for the treatment of cancer. Hyperthermia therapy
is used to kill cancer directly and increase the effectiveness of
companion radiation treatments. Research has also shown promising
results from the use of hyperthermia therapy in combination with
chemotherapy, and for tumor reduction prior to surgery. For further
information visit BSD Medical's website at www.BSDMedical.com or BSD's
patient website at www.treatwithheat.com.

Statements contained in this press release that are not historical
facts are forward-looking statements, as defined in the Private
Securities Litigation Reform Act of 1995. All forward-looking
statements are subject to risks and uncertainties detailed in the
Company's filings with the Securities and Exchange Commission.

http://www.eurekalert.org/pub_releases/2006-11/eofr-frt110906.php

Public release date: 10-Nov-2006

Contact: Emma Mason
wordmason@mac.com
44-077-112-96986
European
Organisation for Research and Treatment of Cancer

First report that apoptotic and anti-angiogenic
therapies work better together than alone

Prague, Czech Republic: American researchers have found that giving
a combination of imantanib (Glivec [1]) and a drug that induces cell
death (apoptosis) was better at inhibiting the growth of Ewing's
sarcoma in mice than either therapy on its own.

Imantanib works by preventing the creation of new blood vessels to
supply the growing tumour (anti-angiogenesis) and the researchers
believe that this is the first report of synergy between apoptosis and
anti-angiogenic therapy in pre-clinical work.

Professor Andrea Hayes-Jordan reported to the EORTC-NCI-AACR [2]
Symposium on Molecular Targets and Cancer Therapeutics in Prague today
(Friday 10 November) that treating sarcoma cells with imantanib
inhibited a growth factor called PDGFR-beta. This had the effect of
increasing the sensitivity of the cells to a drug called tumour
necrosis factor-related apoptosis-inducing ligand (TRAIL).

Prof Hayes-Jordan, assistant professor of surgery and pediatrics at
the MD Anderson Cancer Center, Houston, USA, said: “When I treated the
tumour cells with imantanib, the anti-angiogenic drug, the receptors
for TRAIL, the apoptotic drug, increased, thus increasing the efficacy
of TRAIL. This was supported by the mouse studies, which showed
increased inhibition of pulmonary metastases and primary tumour growth
when both were used simultaneously. These findings are important
because, if it proves to be effective in humans, it would be well
tolerated and have significantly fewer side effects than traditional
cytotoxic therapy. Also, at present, we have no effective chemotherapy
for pulmonary metastases – the only effective treatment is surgery – so
this would give us another option.”

Prof Hayes-Jordan hopes to investigate the dual therapy in humans in
a clinical trial within 12-18 months.

http://www.clinicaltrials.gov/ct/show/NCT00365872?order=37

External Beam Radiation With Intratumoral Injection Of Dendritic Cells
As Neo-Adjuvant Treatment for Sarcoma

This study is currently recruiting patients.
Verified by H. Lee Moffitt Cancer Center and Research Institute August
2006
Sponsors and Collaborators:     H. Lee Moffitt Cancer Center and
Research Institute
Cancer Treatment Research Foundation
Information provided by:     H. Lee Moffitt Cancer Center and Research
Institute
ClinicalTrials.gov Identifier:     NCT00365872

Purpose

This is a Phase II study using a combination of external beam radiation
with intratumoral injection of dendritic cells (white blood cells) as
neo-adjuvant treatment for patients with high-risk soft tissue sarcoma.
The purpose is to determine if an injection of the patient’s own immune
related white blood cells into their tumor will strengthen the immune
system to fight against their cancer.

Pre-treatment tests include a blood draw for anti-tumor immune response
and Hepatitis B, Hepatitis C, HIV tests. Labs are drawn for baseline
immunity assays; pre-treatment biopsy with collection of tumor cells,
immunological studies, surgical specimen and post-therapy immunity
assays.

Conventional therapy on day 1 is the external beam radiation which will
be delivered in 25 equal fractions – daily for 5 days (M-F) over a
5-week period. Experimental therapy consists of leukapheresis which is
the separation and removal of leukocytes from withdrawn blood, frozen
for later use. There will be four DC injections occurring during the
course of the external beam radiation therapy.

DCs will be labeled (with a radioisotope) and injected intratumorally
before surgery. You will be randomized into one of three groups. One
group will receive injection of labeled DCs 72 hrs before surgery,
second group – 48 hrs, and third group 24 hrs before surgery. On day 50
of treatment,surgery will be performed to remove the tumor.

Results will be correlated with the level of specific immune response.
If the experimental treatment causes a measurable change in the immune
blood tests, there will be office visits, every 3 months for 2 years.
In the longer term, there will be office visits at 6 month intervals
for the third year, and yearly thereafter. A CT scan of chest and MRI
scan of extremity will be performed at every office visit.
Condition     Intervention     Phase
Soft Tissue Sarcoma
     Vaccine: Dendritic cell injections
 Procedure: Radiation therapy
 Procedure: Surgery for tumor removal
    Phase II

MedlinePlus related topics:  Soft Tissue Sarcoma
Genetics Home Reference related topics:  Soft Tissue Sarcoma

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Uncontrolled, Single
Group Assignment, Safety/Efficacy Study

Official Title: Combination of External Beam Radiation With
Intratumoral Injection of Dendritic Cells as Neo-Adjuvant Treatment of
High-Risk Soft Tissue Sarcoma Patients
Further study details as provided by H. Lee Moffitt Cancer Center and
Research Institute:
Primary Outcomes: Determine if combined neo-adjuvant treatment with
apoptosis-inducing therapy (gamma-irradiation) plus intratumoral DC
administration will induce a T lymphocyte immune response specific for
soft tissue sarcoma associated antigens.; Study the functional activity
of T cells, as well as the presence, and function of DCs in patients
treated with combined administration of apoptosis-inducing agents and
DCs.; Assess the toxicity of the investigational treatment, and the
primary tumor responses.; Analysis of DC migration will compare the
ratio of radioactive count within lymph nodes and the tumor site to the
background counts.
Expected Total Enrollment:  22

Study start: June 2006

This is a Phase II study using a combination of external beam radiation
with intratumoral injection of dendritic cells (white blood cells) as
neo-adjuvant treatment for patients with high-risk soft tissue sarcoma.
The purpose is to determine if an injection of the patient’s own immune
related white blood cells into their tumor will strengthen the immune
system to fight against their cancer.

Pre-treatment test will consist of a blood draw for anti-tumor immune
response and Hepatitis B, Hepatitis C, HIV tests. A biopsy with
collection of tumor cells. Assays (ELISPOT and flow cytometry) to test
for the intended anti-tumor cell T cell response will be performed on
biopsy specimens as well as standard pathology department review of
specimens for diagnosis and assessment of necrosis and apoptosis. Labs
are also drawn for surgical specimens and post-therapy immunity assays.

Prior to commencing therapy, a procedure called leukapheresis
(peripheral blood mononuclear cell) isolation will be conducted and
twenty-four hours prior to intended injection, the dendritic cells will
be harvested and assessed for quality control. Prior to injection (the
clinical target is the gross tumor), history and physical examination
will be performed. Toxicity will be assessed according to CTC criteria.
The plan will be to inject the entire dendritic cell product evenly
throughout the tumor.

Conventional therapy consists of external beam radiation therapy, 25
fractions from day 1-33 administered Monday through Friday only. The
experimental therapy, dendrite cell (DC) injections will occur during
the course of the external beam radiation therapy. DC injections will
be prepared from frozen white blood cells and injected at four
intervals on day 12, 19, 26, and day 33.

DCs will be labeled (with a radioisotope) and injected intratumorally
before surgery. You will be randomized into one of three groups. One
group will receive injection of labeled DCs 72 hrs before surgery,
second group – 48 hrs, and third group 24 hrs before surgery. Surgery
will occur on day 50 for tumor removal.

If the experimental treatment causes a measurable change in the immune
blood tests, there will be office visits, every 3 months for 2 years.
In the longer term, there will be office visits at 6 month intervals
for the third year, and yearly thereafter. A CT scan of chest and MRI
scan of extremity will be performed at every office visit.

Eligibility
Genders Eligible for Study:  Both
Criteria

Inclusion Criteria:

    * Histologically diagnosed high-grade (intermediate or high grade)
soft tissue sarcoma of clinical and radiographic histological lineage.
    * Musculoskeletal tumor in extremities, trunk or chest wall.
    * Primary tumor or isolated locally recurrent tumor greater than 5
cm in diameter.
    * Clinical Stage T2N0M0 or T3N0M0
    * Patient is not a candidate for neoadjuvant chemotherapy.
    * Performance status ECOG 0 or 1.
    * No steroid therapy within 4 weeks of first dendritic cell
administration.
    * No coagulation disorder.
    * Patient’s written informed consent.
    * No contraindication to resection.
    * Adequate organ function (measured within a week of beginning
treatment).
    * WBC > 3,000/mm to the third power and ANC >1500/mm to the
third power
    * Platelets > 100,000/mm to the third power
    * Hematocrit > 25%
    * Bilirubin < 2.0 mg/dL
    * Creatinine < 2.0 mg/dL, or creatinine clearance > 60 mL/min

Exclusion Criteria:

    * Retroperitoneal location.
    * Gastrointestinal stromal tumor (GIST).
    * Demonstrated metastatic disease.
    * Prior radiation therapy if the current tumor is locally recurrent
after prior resection.
    * Concurrent treatment with any anticancer agent other than
radiation as dictated by the protocol.
    * Bleeding disorder.
    * H.I.V. infection or other primary immunodeficiency disorder.
    * Ongoing systemic therapy with immunosuppressant drugs (e.g.
corticosteroids, azathioprine, cyclosporin, methotrexate).
    * Any serious ongoing infection.
    * Pregnant or lactating women — Patients in reproductive age must
agree to use contraceptive methods for the duration of the study (a
pregnancy test will be obtained before treatment).
    * ECOG performance status of 2, 3 or 4.

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier  NCT00365872

Mary N Dunn, CRN      813-745-8356    dunnmn@moffitt.usf.edu

Florida
      H. Lee Moffitt Cancer Center & Research Institute, Tampa, 
Florida,  33612,  United States; Completed

      H Lee Moffitt Cancer Center & Research Institute, Tampa, 
Florida,  33612,  United States; Recruiting

Study chairs or principal investigators

Scott Antonia, M.D.,  Principal Investigator,  H. Lee Moffitt Cancer
Center and Research Institute  

More Information

Active
Clinical Trials at Moffitt Cancer Center

Study ID Numbers:  MCC-14497
Last Updated:  August 18, 2006
Record first received:  August 17, 2006
ClinicalTrials.gov Identifier:  NCT00365872
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2006-09-25

http://www.jco.org/cgi/content/abstract/24/24/3997

Impact of High-Dose Busulfan Plus Melphalan As Consolidation in
Metastatic Ewing Tumors: A Study by the Société Française des Cancers
de l'Enfant

Journal of Clinical Oncology, Vol 24, No 24 (August 20), 2006: pp.
3997-4002
© 2006 American Society of Clinical Oncology
DOI: 10.1200/JCO.2006.05.7059

Odile Oberlin, Annie Rey, Anne Sophie Desfachelles, Thierry Philip,
Dominique Plantaz, Claudine Schmitt, Emmanuel Plouvier, Odile Lejars,
Hervé Rubie, Philippe Terrier, Jean Michon

From the Departments of Paediatric Oncology, Biostatistics, and
Pathology, Institut Gustave Roussy, Villejuif; Department of Paediatric
Oncology, Centre Oscar Lambret, Lille; Department of Paediatric
Oncology, Centre Léon Bérard, Lyon, France; Department of Paediatric
Oncology, Hôpital Michalon, Grenoble; Department of Paediatric
Oncology, Hôpital d'enfants, Nancy; Department of Paediatric Oncology,
Centre hospitalo-universitaire, Besançon; Department of Paediatric
Oncology, Hôpital Clocheville, Tours; Department of Paediatric
Oncology, Hôpital Purpan, Toulouse; and the Department of Paediatric
Oncology, Institut Curie, Paris, France

Address reprint requests to Odile Oberlin, MD, Department of Paediatric
Oncology, Institut Gustave-Roussy, Rue Camille Desmoulins, 94805
Villejuif Cedex, France; e-mail: oberlin@igr.fr

PURPOSE: To improve the prognosis for patients with metastatic Ewing
sarcoma/primitive neuroectodermal tumors (ES/PNET) using conventional
chemotherapy and consolidation high-dose chemotherapy (HDCT) containing
busulfan and melphalan.

PATIENTS AND METHODS: Ninety-seven unselected patients with newly
diagnosed metastatic ES/PNET received induction chemotherapy that
included five cycles of cyclophosphamide 150 mg/m2/d for 7 days,
doxorubicin 35 mg/m2/d once, followed by two cycles of ifosfamide 1.8
g/m2/d for 5 days, and etoposide 100 mg/m2/d for 5 days. Patients in
complete or very good partial remission received HDCT with busulfan
total dose 600 mg/m2 and melphalan 140 mg/m2 followed by autologous
blood stem cells. Local therapy (surgery and/or radiation therapy) was
performed before or after HDCT.

RESULTS: Ninety-seven patients were enrolled from 1991 to 1999 (median
age, 12.3 years; range, 0.2 to 25 years). Among them, 75 received HDCT.
The 5-year event-free survival (EFS) rate for all 97 patients was 37%
and the overall survival (OS) rate was 38%. The EFS after HDCT was 47%.
The EFS for the 44 patients with lung-only metastases was 52%, whereas
it was 36% for patients with bone metastases without bone marrow
involvement. Among the 23 patients with bone marrow metastases, only
one survived. The multivariate analysis for both EFS and for OS
identified three independent prognostic factors: age, fever at
diagnosis, and bone marrow involvement.

CONCLUSION: Compared with conventional chemotherapy, HDCT may yield
benefits for patients with lung-only metastases or bone metastases.
These results warrant confirmation in a randomized trial and provide
part of the background data for the ongoing Euro-Ewing study.

Supported by Institut Gustave Roussy and by Société Française des
Cancers de l'Enfant.

Authors' disclosures of potential conflicts of interest and author
contributions are found at the end of this article.

http://clinicaltrials.mayo.edu/clinicaltrialdetails.cfm?trial_id=100300

The Use of Chemotherapy Medications, Gemcitabine (Gemzar) and Docetaxel

(Taxotere) in the Treatment of Ewing's Sarcoma, Osteosarcoma, or

Chondrosarcoma

IRB Number : 1693-05

Trial Status : Open for Enrollment

Phase: II

Why is this study being done?

This study is being done to:

-See if the chemotherapy drugs gemcitabine (Gemzar) and docetaxel

(Taxotere), when given together, may help to fight cancer of the bone or

soft tissue. Each of these drugs is approved by the US Food and Drug

Administration (FDA) for the treatment of some kinds of cancer, such as

cancer of the pancreas and lung, but they are not approved for this type

of cancer, so in this study they are called investigational drugs.

-See what effects (good and bad) gemcitabine and docetaxel have on the

patient and the tumor.

-See how a patients body processes the gemcitabine and docetaxel.

-(When possible), to do genetic research studies on a sample of a

patients tumor tissue.

Who is Eligible to Participate in the Study?

-Patients diagnosed with Ewings sarcoma or Osteosarcoma, and have

received standard treatments for this type of cancer, but the tumor has

come back after treatment.

-Patients diagnosed with chondrosarcoma and the tumor cannot be

completely removed by surgery or has come back after surgery.

– Patients age 4 and older

-No prior treatment with gemcitabine or taxanes

*More specific, detailed eligibility and/ or exclusion criteria are

associated with this trial.

What is Involved With this Study?

-Medication given through a vein 2 times in a 3 week cycle, for up to 14

cycles

-Physical Exams

-Weekly Blood Tests

-X-rays, CT scans, MRI scans and/ or nuclear medicine scans including a

bone scan to measure patients tumor

How long will the Study run?

Patients will be in the study and receive treatment as long as the tumor

has stayed the same or has gotten smaller and patient has not had any

bad side effects, for up to 14 cycles (each cycle is 3 weeks). Treatment

will be stopped if patients tumor gets larger, if bad side effects, if

doctor thinks further treatment would not be in patients best interest,

if study closes, or if patient chooses to stop treatment.

Sponsor(s): MD Anderson Cancer Center

Study Activation: 12-19-2005

IRB Review and Approval Date: 9-8-2005

Study Type: Treatment

Projected Accrual: 10 patients

Costs of Study:There may be standard patient care costs related to

participating in a cancer research study.

Principal Investigator: Dr. Scott Okuno

Who can I Contact for Additional Information on this Trial?

If you are interested in participating in this study or would like

additional information, please contact Mayo Clinic's Cancer Center

Clinical Trials Referral Coordinator at (507) 538-7623.

What is/are the Locations of this Clinical Trial?

Rochester, MN