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Trial Title:
Synchrotron Radiation to the Treatment of Intracranial Tumors
NCT ID:
NCT01640509
Condition:
Brain Cancer
Conditions: Official terms:
Brain Neoplasms
Conditions: Keywords:
Radiotherapy, Targeted
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Unknown status
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Radiation
Intervention name:
treated by synchrotron radiation
Description:
treated by synchrotron radiation
Arm group label:
synchrotron radiation
Summary:
The purpose of this study is to prove the safety and acceptability of treatment with the
Synchrotron radiation by medium-term medical follow-up of the patients.
Detailed description:
Synchrotron radiation (SR) is used to produce monochromatic X-ray photons of very high
intensity with tunable energy in the range of medium energies (0-150 keV). Thus freed of
low energies, the penetration is still important and the types of possible interactions
are, in addition to the Compton Effect in water, the photoelectric effect with any atom
much heavier than those of the living mater represented by the carbon, oxygen, hydrogen,
nitrogen and phosphorus. Photoelectric interactions cause energy deposits much larger
than the Compton Effect, but they require the presence of foreign atoms in living tissue
to occur. It may be, for example iodine, platinum or gadolinium, all these atoms are
commonly introduced into the human body in medical practice as contrast media in
radiology, or as anti-neoplastic chemotherapy.
The use of SR for radiotherapy, if you want to take advantage of its original properties,
needs the use of a combined treatment: radiation plus medication bringing the heavy atoms
suitable for photo electric effect. Such a concept of combined therapy is widely used in
radiotherapy for decades and was the source of many advances in treatment, some are
presently routine practices (chemo-radiotherapy, photodynamic therapy) other are still
under study as translational research (boron neutron capture therapy). The SR photons at
these "photoelectric" energy band can cause highly cytotoxic damages in tumors especially
when treated with platinum (cisplatin or carboplatin). Indeed, they provide a
photoelectric activation of platinum atoms leading to a massive energy deposition in the
DNA of tumors. This therapeutic principle has been called platinum photoactivation
therapy (PAT-plat). It is particularly suitable for tumors of small to medium volumes,
localized small to medium-depth and suitable for a multi-beam ballistics. Also if there
is a possibility of loading the tumor tissue with high doses of heavy compounds to
achieve the combined treatment in favorable conditions, one would expect a greater
therapeutic effect than conventional treatments. Brain tumors represent a model with
these features, thanks to recent techniques of convection enhanced delivery (CED), which
allow a direct infusion of medication in the tumor.
This work is not conceptually particularly complex although technically sensitive and
very original since ESRF and the Grenoble University Hospital are the only institution
which have made the effort to date to develop in close cooperation a SR line entirely
devoted to biomedical research. There is no other site in the world is this situation,
most of the other centers have either lower energies, or do not have the immediate
vicinity of an academic medical center that can set up the collaboration needed or are
too new to have already reached this experimental level. On the other hand, the technical
and material investments are rather important and as information flow is very free, it
was not considered appropriate at this time to start such research simultaneously in
several sites. The ESRF and the RSRM team ("Rayonnement Synchrotron et Recherche
Médicale") are therefore pioneers in this field and their work is well known worldwide.
The 2010 Equipex call for tender agreed to fund the first table top synchrotron prototype
to be designed and assembled in Orsay : ThomX project at the LAL, laboratoire de
l'accélérateur linéaire, our team is associated to this development. Our technique might
spread outside the domain of the great instruments [http://sera.lal.in2p3.fr/thomx/]..
To carry out the treatment with a satisfactory distribution of the dose of SR, it is
necessary to increase the stopping power of the target tumor by the use of an injection
of iodinated contrast medium at the time of irradiation. This treatment can be applied to
any tumor having good contrast uptake at CTscan and incidentally which may be treated
with platinum. For these reasons, the anatomical location of intracranial human tumors
has been chosen for the study of the application of this treatment with SR monochromatic
80 keV.
The experimental treatment will be a part of standard treatment for brain metastases
under conformal radiotherapy or stereotactic. This irradiation will complement a
pan-encephalic standard irradiation that will be made later, thus providing additional
security in terms of dosimetry.
Main objective: To prove the safety and acceptability of treatment with the SR by
medium-term medical follow-up of the patients.
Primary outcome: limiting adverse events will be judged according to international scales
appropriate to the post-irradiation "acute" toxicity: radiation therapy and / or
chemo-radiotherapy NCI-CTC scale; post- irradiation "late" toxicity radiation therapy and
/ or chemo-radiotherapy SOMA-LENT scale. The acceptable limit for these two criteria will
be grade <3; performance status (WHO scale).
Secondary objectives:
Evaluate limiting adverse events free survival (EIL) "severe" and "late", related to
treatment.; to evaluate the disease-free survival of the treated site; to evaluate the
intracranial disease-free survival (absence of new metastases); to evaluate the antitumor
efficacy assessed by morphological objective response (complete response and partial
response) to treatment by RECIST.
The objective of this study is to demonstrate the ability to deliver reliable, secure and
efficient radiation by synchrotron radiation under dosimetry conditions similar to the
techniques of advanced radiation therapy with high-energy photons. It will thus be a
"platform" for future experimental test of new concepts of combined treatment with in
situ administration of vectors molecules of heavy atoms by CED.
This is a study without any control group that will evaluate each patient's response
according to RECIST criteria and record limiting adverse events (EIL), acute and late, by
an independent external evaluation. Patients will have an initial phase of radiation at
the ESRF to be followed by an additional irradiation at the University Hospital.
The study will be carried out in several successive steps, each including the number of
patients needed to achieve the proposed objective. The number of patients will be three
for each increment, unless extended for a particular level because of toxicity. Assuming
an uneventful progression of the entire protocol described below, a total of 50 patients
are to be included in this study in two to three years.
These steps are:
- Verification of the reproducibility of the kinetics of iodinated contrast in the
tumor.
- Introduction of an iodinated contrast agent IV with a single-dose irradiation by SR.
- Dose escalation (Iodine and SR) and fractionation.
- Introduction of a platinum-injection system with the ultimate optimized RS protocol.
- Optimizing the dose of platinum by an advanced method of administration (CED or
double platinum protocol).
The transition from one step to the next will be dependent on the feasibility of the
previous step, the frequency and severity of side effects occurred at each step of the
protocol. An External Review Committee will monitor the progress of the study and propose
appropriate changes or discontinuation of the trial if appropriate.
The ESRF and the CHU of Grenoble have settled a cooperation agreement since the building
of ESRF in the 80ties to develop medical application of SR: "RSRM". In 2003 the
scientific team of the CHU and the University Joseph Fourier of Grenoble become an INSERM
unit devoted to RSRM with the experimental medical imaging and radiotherapy with SR as a
main goal: the different research axis of the Unit have been organized to contribute to
these two domains and for each a specific department of the CHU has been associated. For
the experimental medical imaging: the neuro-radiology and the cardiology departments; for
experimental radiotherapy: the radiation oncology department of the CHU. That one is
tidily associated: the patients will be selected, recruited, hospitalized, imaged and
treated under the responsibility of the MD and the medical physicists of this CHU
department and the patients will be transported for irradiation at the experimental
irradiation room at ESRF for a part of their irradiation plan. This way, this first
attempt of SR application to cancer treatment is completely embedded in the scientific
and technical development of SR at ESRF which has invested large amount of money since
years to modify, upgrade and equipped its biomedical facility.
This pioneer activity is followed by an industrial development of know how to make
possible the future use of SR if it should issue significant and valuable progress. This
effort, so far, has given way to the ThomX project.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Controlled tumor disease in the primary site and no syndrome metastatic extracranial
threatening short-term
- Presence of 1 to 3 metastases brain symptomatic or not, metachronous primary cancer
of a solid, proven itself by histopathological examination
- In case of multiple lesions sites must be sufficiently spaced so that the PTV can be
in separate horizontal planes
- PS < 2
Exclusion Criteria:
- One or more lesions > 3 cm in diameter on MRI, or infratentorial location
- Performed surgical resection or formal indication
- In progress or finished chemotherapy within the last 4 weeks
- Partial or total irradiation of brain in the past , or total body irradiation
- Presence of a second cancer that would be likely to render uncertain the
identification of the origin of metastases
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Esrf / Id17
Address:
City:
Grenoble
Zip:
38000
Country:
France
Status:
Recruiting
Start date:
June 2012
Completion date:
June 2019
Lead sponsor:
Agency:
University Hospital, Grenoble
Agency class:
Other
Source:
University Hospital, Grenoble
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT01640509
http://www.chu-grenoble.fr/