Brain MetastasesPhase 2NCT00805636
Evaluation of the Efficacy and Safety of [18F]-ML-10, as a PET Imaging Radiotracer, in Early Detection of Response of Brain Metastases of Solid Tumors to Radiation Therapy.
A Phase 2 study testing 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10), Stereotactic Radio-Surgery (SRS) therapy and Positron Emission Tomography in people with Brain Metastases and Solid Tumors, run by Aposense Ltd. at 4 sites in United States.
Trial summary
The purpose of this study is to evaluate the potential of [18F]-ML-10 to serve as an imaging tool for the early detection of response of brain metastases to radiation therapy. Such early detection may help early identification of responsive and non-responsive lesions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Brain Metastases, Solid Tumors
- What is being tested?
- 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10), Stereotactic Radio-Surgery (SRS) therapy and Positron Emission Tomography
- Type of treatment
- Injection or infusion, Surgery or procedure
- How many people
- 30 participants
- Where
- 4 sitesUnited States
- Study dates
- Nov 2008to Oct 2010
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients with metastatic non- hematological solid tumors, with one or more brain metastases, of which at least one lesion has a diameter ≥1.5 cm, as confirmed by anatomical imaging (GBCA-enhanced MRI), wherein this lesion (or lesions) is scheduled to be treated by SRS.
- ECOG performance status of 0, 1 or 2 at the time of enrollment.
- Women of child-bearing potential must have a negative blood pregnancy test at screening and use an adequate and medically acceptable contraceptive method.
- Willing and able to follow the protocol requirements.
- Able to provide written informed consent.
Who cannot join
- Unstable medical condition, such as ischemic heart disease, or any other disease or medical condition that may place the patient at added risk during the study, as assessed by the Principal Investigator. A patient with a seizure disorder, focal or generalized, not adequately controlled by anti-convulsant therapy, and /or patient who have experienced an event of focal or generalized seizure within 7 days prior to screening will be considered neurologically unstable.
- Any indication of a risk for an imminent brain herniation, as evaluated by the Principal Investigator, based on the findings on brain MRI.
- Treatment with whole brain radiation therapy (WBRT) within 3 months prior to screening.
- Evidence for hemorrhage within any of the brain metastases.
- Any known psychiatric disorder other than mild depression or anxiety that may affect adherence to the study requirements.
- Known allergy to gadolinium.
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- Any contraindication to MR imaging (e.g., metal implant, aneurysm clip, pacemaker).
- Other condition that, in the opinion of the Investigator, might jeopardize the safety of the patient, or the adequate evaluation of study results.
- Treatment with any investigational drug, device or biologic agent within 30 days prior to administration of [18F]-ML-10.
Trial locations and contacts
4 sites in 1 country.
United States4 sites, 4 recruiting
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Juho Whang, jwhang@bidmc.harvard.edu
Eric Wong, MD
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Elysia Larson, ELARSON@LROC.HARVARD.EDU
Stephanie E Weiss, MD
- Recruiting
Department of Radiation oncology, Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Gina Giannantoni-ibelli, GiannanG@mskcc.org
Kathryn Beal, MD
- Recruiting
UPMC Shadyside Radiation Oncology
Pittsburgh, Pennsylvania, 15232
Rhonda Berlin, berlinrL@upmc.edu
Heron Dwight, MD
About this study
Official title: Evaluation of Efficacy and Safety of 18FML10, as a PET Imaging Radiotracer, in Early Detection of Response of Brain Metastases of Non-Hematological Solid Tumors to Radiation Therapy
The purpose of this study is to evaluate the potential of [18F]-ML-10 to serve as an imaging tool for the early detection of response of brain metastases to radiation therapy. Such early detection may help early identification of responsive and non-responsive lesions. The experimental design of the present study aims to evaluate the potential of PET imaging with [18F]-ML-10 to address the currently unmet clinical need for very early (within one day)assessment of response to therapy. Currently, response assessment is available only after several weeks or months after completion of therapy, when tumor shrinkage can be detected by anatomical imaging (by MRI). Early detection of tumor response to treatment is now widely-recognized as a highly-desirable goal in oncology, and is respectively the target of intense research worldwide. In the future, the option to know early upon treatment administration, that the treated tumor is a non-responsive, may improve clinical management of patients with brain metastases of solid tumors.
Read the detailed description
Early assessment of the efficacy of anti-cancer therapy is highly desirable and an unmet need in clinical oncology. Currently, treatment efficacy is mostly measured by following tumor size by anatomical imaging (CT scan or MRI). However, changes in tumor size may be observed only after several weeks to several months after completion of treatment. Meanwhile, in cases where there is no response, the patient is unnecessarily exposed to treatment's side effects, and precious time may be lost before the initiation of an alternative, potentially more beneficial line of therapy. Therefore, there is an urgent and serious need for better tools for monitoring of tumor response to anti-cancer treatments.
To address this need, [18F]-ML-10, a novel small molecular-weight probe (MW 205) was developed for clinical detection of apoptosis in vivo by positron emission tomography (PET). [18F]-ML-10 is a member of the Aposense family of compounds, a novel class of molecular probes for molecular imaging of cell death. The proposed indication for which [18F]-ML-10 is being developed is for early assessment of response of solid tumors to radiation and chemoradiation therapy.
Previous preclinical and clinical studies have substantiated the safety of [18F]-ML-10, its very high stability in vivo, its favorable biodistribution profile, and its efficacy in clinical detection of cell death. In preclinical studies, the selective retention of [18F]-ML-10 in the focus of the neurovascular cell death in cerebral ischemia was demonstrated in respective animal models. [18F]-ML-10 has been examined in two clinical trials in Uppsala Imanet, Sweden, and has been found safe in administration to healthy subjects and to elderly subjects with acute ischemic cerebral stroke. In these clinical trials, [18F]-ML-10 was also found efficacious in the clinical imaging of apoptosis, being either physiological apoptosis as observed in the testes in young healthy males, and pathological cell death, as observed in the brains of patients with acute ischemic cerebral stroke.
Additional Phase 2 study demonstrated the suitability and safety of 18F-ML-10, designed to serve as a PET radiotracer for early detection of cellular apoptosis of brain metastases in response to WBRT. The relationship between the early change in 18F-ML-10 uptake by the tumor, observed during or upon completion of treatment, and subsequent tumor shrinkage as observed by MRI eight weeks after the completion of WBRT, was demonstrated.18F-ML-10 demonstrated a good safety profile with no drug-related AEs or any effect on safety parameters.
- Conditions
- Brain Metastases, Solid Tumors
- Being tested
- 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10), Stereotactic Radio-Surgery (SRS) therapy, Positron Emission Tomography
- Keywords
- cell death, PET imaging, brain metastases, stereotactic radiosurgery
- Medical subject headings
- Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10)Drug
Also called [18F]-ML-10
[18F]-ML-10 will be radiolabeled at the PET Radioactive Drug Production (RDP) facility at or in close proximity to each clinical site, and will be administered as an intravenous bolus injection (in 3-10 ml sterile saline solution, containing no more than 10% ethanol by volume). The dose concentration selected for [18F]-ML-10 will be 7 MBq/Kg or 0.19 mCi/Kg. The radioactivity dosage of [18F]-ML-10 administered at each PET/CT session will be at least 300 MBq (8.1 mCi) and not more than 500 MBq (13.5 mCi).
Stereotactic Radio-Surgery (SRS) therapyRadiation
SRS will be administered according to the standard of care using a radiation dose of 14-24 Gy to each lesion.
Positron Emission TomographyProcedure or surgery
Each patient will undergo 2 PET/CT sessions, each following intravenous administration of [18F]-ML-10, to assess tracer uptake by the brain metastases treated by SRS. The PET/CT scan will be directed to the brain and will include one bed position. The PET/CT sessions will be performed at baseline, i.e., before the radiation treatment, and on the day after, within 24h after SRS treatment.
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the relationship between changes in 18FML10 uptake in the target lesions (PET/CT) obtained before and after radiotherapy (SRS), and changes of the lesions size (MRI, ~8w after SRS) in response to treatment, according to the WHO criteria
Measured: 1 year
Secondary outcomes (3)
Characterization of early alterations in the voxel-based 18FML10 uptake in the target lesion in response to the single fraction high-dose Stereotactic RadioSurgery, SRS. 18FML10 uptake at 24h after SRS and at baseline, before SRS, will be compared
Measured: 1 year
To identify parameters derived from the changes in 18FML10 uptake observed early after SRS that can discriminate responsive from non-responsive target lesions, and to estimate optimal cut-off values of this parameter (sensitivity and specificity)
Measured: 1 year
To perform additional analyses for all other lesions with longest diameter ≥ 1.5 cm treated by SRS.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2008 (estimated)
- Study startNov 2008
- Primary completionOct 2010 (estimated)
- Study completionOct 2010 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain MetastasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aposense Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00805636
- Sponsor's protocol ID
- NST-CA004CTIL
- Status last verified
- Apr 2010
- First submitted
- 7 Dec 2008
- Last updated
- 12 May 2010
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Efficacy and Safety of 18FML10, as a PET Imaging Radiotracer, in Early Detection of Response of Brain Metastases of Non-Hematological Solid Tumors to Radiation Therapy
- ClinicalTrials.gov ID
- NCT00805636
- Acronym / sponsor ID
- NST-CA004CTIL
- Conditions
- Brain Metastases, Solid Tumors
- Keywords
- cell death, PET imaging, brain metastases, stereotactic radiosurgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Aposense Ltd.Industry (pharma, biotech, devices)
- Study start
- Nov 2008
- Primary completion
- Oct 2010 (estimated)
- Study completion
- Oct 2010 (estimated)
- First posted
- 9 Dec 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the potential of [18F]-ML-10 to serve as an imaging tool for the early detection of response of brain metastases to radiation therapy. Such early detection may help early identification of responsive and non-responsive lesions. The experimental design of the present study aims to evaluate the potential of PET imaging with [18F]-ML-10 to address the currently unmet clinical need for very early (within one day)assessment of response to therapy. Currently, response assessment is available only after several weeks or months after completion of therapy, when tumor shrinkage can be detected by anatomical imaging (by MRI). Early detection of tumor response to treatment is now widely-recognized as a highly-desirable goal in oncology, and is respectively the target of intense research worldwide. In the future, the option to know early upon treatment administration, that the treated tumor is a non-responsive, may improve clinical management of patients with brain metastases of solid tumors.
Detailed description
Early assessment of the efficacy of anti-cancer therapy is highly desirable and an unmet need in clinical oncology. Currently, treatment efficacy is mostly measured by following tumor size by anatomical imaging (CT scan or MRI). However, changes in tumor size may be observed only after several weeks to several months after completion of treatment. Meanwhile, in cases where there is no response, the patient is unnecessarily exposed to treatment's side effects, and precious time may be lost before the initiation of an alternative, potentially more beneficial line of therapy. Therefore, there is an urgent and serious need for better tools for monitoring of tumor response to anti-cancer treatments.
To address this need, [18F]-ML-10, a novel small molecular-weight probe (MW 205) was developed for clinical detection of apoptosis in vivo by positron emission tomography (PET). [18F]-ML-10 is a member of the Aposense family of compounds, a novel class of molecular probes for molecular imaging of cell death. The proposed indication for which [18F]-ML-10 is being developed is for early assessment of response of solid tumors to radiation and chemoradiation therapy.
Previous preclinical and clinical studies have substantiated the safety of [18F]-ML-10, its very high stability in vivo, its favorable biodistribution profile, and its efficacy in clinical detection of cell death. In preclinical studies, the selective retention of [18F]-ML-10 in the focus of the neurovascular cell death in cerebral ischemia was demonstrated in respective animal models. [18F]-ML-10 has been examined in two clinical trials in Uppsala Imanet, Sweden, and has been found safe in administration to healthy subjects and to elderly subjects with acute ischemic cerebral stroke. In these clinical trials, [18F]-ML-10 was also found efficacious in the clinical imaging of apoptosis, being either physiological apoptosis as observed in the testes in young healthy males, and pathological cell death, as observed in the brains of patients with acute ischemic cerebral stroke.
Additional Phase 2 study demonstrated the suitability and safety of 18F-ML-10, designed to serve as a PET radiotracer for early detection of cellular apoptosis of brain metastases in response to WBRT. The relationship between the early change in 18F-ML-10 uptake by the tumor, observed during or upon completion of treatment, and subsequent tumor shrinkage as observed by MRI eight weeks after the completion of WBRT, was demonstrated.18F-ML-10 demonstrated a good safety profile with no drug-related AEs or any effect on safety parameters.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients with metastatic non- hematological solid tumors, with one or more brain metastases, of which at least one lesion has a diameter ≥1.5 cm, as confirmed by anatomical imaging (GBCA-enhanced MRI), wherein this lesion (or lesions) is scheduled to be treated by SRS.
- ECOG performance status of 0, 1 or 2 at the time of enrollment.
- Women of child-bearing potential must have a negative blood pregnancy test at screening and use an adequate and medically acceptable contraceptive method.
- Willing and able to follow the protocol requirements.
- Able to provide written informed consent.
Key exclusion criteria (9 listed)
- Unstable medical condition, such as ischemic heart disease, or any other disease or medical condition that may place the patient at added risk during the study, as assessed by the Principal Investigator. A patient with a seizure disorder, focal or generalized, not adequately controlled by anti-convulsant therapy, and /or patient who have experienced an event of focal or generalized seizure within 7 days prior to screening will be considered neurologically unstable.
- Any indication of a risk for an imminent brain herniation, as evaluated by the Principal Investigator, based on the findings on brain MRI.
- Treatment with whole brain radiation therapy (WBRT) within 3 months prior to screening.
- Evidence for hemorrhage within any of the brain metastases.
- Any known psychiatric disorder other than mild depression or anxiety that may affect adherence to the study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10)Also: [18F]-ML-10[18F]-ML-10 will be radiolabeled at the PET Radioactive Drug Production (RDP) facility at or in close proximity to each clinical site, and will be administered as an intravenous bolus injection (in 3-10 ml sterile saline solution, containing no more than 10% ethanol by volume). The dose concentration selected for [18F]-ML-10 will be 7 MBq/Kg or 0.19 mCi/Kg. The radioactivity dosage of [18F]-ML-10 administered at each PET/CT session will be at least 300 MBq (8.1 mCi) and not more than 500 MBq (13.5 mCi). | Drug | – |
| Stereotactic Radio-Surgery (SRS) therapySRS will be administered according to the standard of care using a radiation dose of 14-24 Gy to each lesion. | Radiation | – |
| Positron Emission TomographyEach patient will undergo 2 PET/CT sessions, each following intravenous administration of [18F]-ML-10, to assess tracer uptake by the brain metastases treated by SRS. The PET/CT scan will be directed to the brain and will include one bed position. The PET/CT sessions will be performed at baseline, i.e., before the radiation treatment, and on the day after, within 24h after SRS treatment. | Procedure or surgery | – |
Primary outcome
To assess the relationship between changes in 18FML10 uptake in the target lesions (PET/CT) obtained before and after radiotherapy (SRS), and changes of the lesions size (MRI, ~8w after SRS) in response to treatment, according to the WHO criteria
Time frame: 1 year
3 secondary outcomes
Characterization of early alterations in the voxel-based 18FML10 uptake in the target lesion in response to the single fraction high-dose Stereotactic RadioSurgery, SRS. 18FML10 uptake at 24h after SRS and at baseline, before SRS, will be compared
Time frame: 1 year
To identify parameters derived from the changes in 18FML10 uptake observed early after SRS that can discriminate responsive from non-responsive target lesions, and to estimate optimal cut-off values of this parameter (sensitivity and specificity)
Time frame: 1 year
To perform additional analyses for all other lesions with longest diameter ≥ 1.5 cm treated by SRS.
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Department of Radiation oncology, Memorial Sloan Kettering Cancer Center
New York, United States
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10), Stereotactic Radio-Surgery (SRS) therapy and Positron Emission Tomography in people with Brain Metastases and Solid Tumors, run by Aposense Ltd. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 May 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the relationship between changes in 18FML10 uptake in the target lesions (PET/CT) obtained before and after radiotherapy (SRS), and changes of the lesions size (MRI, ~8w after SRS) in response to treatment, according to the WHO criteria (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2010.