Metastasis to Brain of Unknown PrimaryPhase 2NCT00696943
18F ML-10 for Early Detection of Response of Brain Metastases to SRS
A Phase 2 study testing ([18F]-ML-10) in people with Metastasis to Brain of Unknown Primary, run by Aposense Ltd..
Trial summary
The purpose of this study is to evaluate the potential of [18F]-ML-10 to serve as a non-invasive imaging tool for the early detection of apoptosis in brain metastases in response to radiation therapy, in patients subjected to stereotactic radiosurgery (SRS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastasis to Brain of Unknown Primary
- What is being tested?
- ([18F]-ML-10)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- Jul 2008to Jul 2009
- 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
- The Patient may only be included in the study if ALL of the following statements are fulfilled:
- Male or female patient diagnosed with metastatic non hematological cancer, with up to 4 brain metastases of which at least one has a minimal diameter of 1.5cm , as assessed by MRI (utilized for SRS planning) and is scheduled for SRS. These metastases will be defined as target lesions.
- Patient is ≥ 18 years of age at the time of signature of the informed consent form.
- Fully conscious patient who has been given written and verbal information, and has then provided an informed consent.
- Patient who is able to cooperate with the studies requirements to lie still during PET/CT imaging scans, which may last for up to 3 hours.
- ECOG performance status of 0, 1 or 2 at the time of enrollment.
Show all 13Show fewer
- Patient with life expectancy ≥ 12 weeks.
- Adequate renal function and adequate hepatic function as assessed by standard laboratory criteria and defined as:
- Creatinine clearance ≥ 60 ml/min/1.73m2according to Cockroft \& Gault Formula
- Total bilirubin ≤ 1.5 times the ULN
- Aspargine aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3 times the ULN in patients without liver metastases; ≤ 5 times the ULN in patients with liver metastases
- Serum calcium levels, adjusted to albumin level, within normal limits.
- For a female patient, pregnancy or breast-feeding are restricted. Woman of child bearing potential must have a negative serum pregnancy test at screening.
Who cannot join
- If any apply, the patient must not be included in the study:
- Unstable medical condition, such as severe ischemic heart disease, liver disease or pulmonary disease, which may risk the patient during the study, as judged by the investigator.
- Any indication of imminent brain herniation
- Any known psychiatric disorder other than mild depression or anxiety.
- Known allergy to Gadolinium
- Other condition that might jeopardize the safety of the patient or the evaluation of the study results, as judged by the investigator.
Show all 10Show fewer
- Treatment with any non-marketed investigational drug within 30 days prior to administration of [18F]-ML-10
- Patient who received Whole Brain Radiation Therapy (WBRT) within 6 months prior screening and/or planned to receive WBRT 8 weeks post SRS
- Patient receiving concurrent treatment with temozolamide or planned to receive temozolamide within 8 weeks post SRS
- Woman of child-bearing potential who is not using an adequate and medically acceptable contraceptive method. Men who do not agree to use effective contraception during the study and for a period of 60 days following the last administration of [18F]-ML-10.
About this study
Official title: An Open-label, Multi-center Study to Evaluate [18F]-ML-10 as a PET Imaging Radiotracer for Early Detection of Response of Brain Metastases to Stereotactic Radio Surgery (SRS)
The purpose of this study is to evaluate the potential of [18F]-ML-10 to serve as a non-invasive imaging tool for the early detection of apoptosis in brain metastases in response to radiation therapy, in patients subjected to stereotactic radiosurgery (SRS). Such early detection may improve clinical management of patients with brain metastases, as it may help early identification of non-responders, and subsequently potentially lead to optimization of radiation techniques such as the need for whole brain radiation therapy (WBRT), addition of brain penetrating chemotherapy or an early decision on referral of the patient with non-responsive lesions to surgery or to systemic chemotherapy. The experimental design of the present study aims to evaluate the potential of non-invasive PET examination with [18F]-ML-10, to provide the clinician with an assessment of response early in the course of treatment, via non-invasive molecular imaging of radiation-induced apoptosis. This information on tumor responsiveness is currently available only several weeks to months after completion of radiotherapy.
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 first clinical indication for which [18F]-ML-10 is being developed is imaging of apoptosis in clinical oncology to monitor tumor response to radiation 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.
- Conditions
- Metastasis to Brain of Unknown Primary
- Being tested
- ([18F]-ML-10)
- 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.
([18F]-ML-10)Drug
Also called 2-(5-fluoro-pentyl)-2-methyl-malonic-acid
[18F]-ML-10 was administered as an intravenous bolus injection (in 3-10 ml sterile saline solution, containing no more than 10% ethanol by volume). The radiation dose of [18F]-ML-10 administered at each session was 300-500 MBq (8.1-13.5 mCi).
| Study group | Role | What they receive |
|---|---|---|
| 18F-ML-10, | Experimental | Pre-treatment baseline and post treatment follow-up 18F ML-10 PET/CT sessions. Receives: Drug: ([18F]-ML-10) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of the change in the uptake of [18F]-ML-10 by the target lesion(s) in response to SRS, as observed by comparing the PET/CT scans before and after SRS. Target lesion is defined as having a minimal diameter of 1.5 cm
Measured: 3 months
Secondary outcomes (2)
Assessment of the relationship between the change in uptake of [18F]-ML-10 by the metastatic target lesions as observed in the PET/CT scans obtained before and after irradiation, and shrinkage of the metastatic target lesion, as assessed by MRI.
Measured: 3 months
Evaluation of the safety of [18F]-ML-10 when administered for 3 consecutive PET/CT scans to patients with brain metastases undergoing SRS.
Measured: one month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2009
- Study completionJul 2009
Why it stopped: Replaced by a global study protocol NST-CA004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastasis to Brain of Unknown PrimaryStudies 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
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aposense Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yael Cohen, Study director, Aposense Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00696943
- Sponsor's protocol ID
- NST-CA005CTIL
- Status last verified
- Nov 2008
- First submitted
- 11 Jun 2008
- Last updated
- 15 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multi-center Study to Evaluate [18F]-ML-10 as a PET Imaging Radiotracer for Early Detection of Response of Brain Metastases to Stereotactic Radio Surgery (SRS)
- ClinicalTrials.gov ID
- NCT00696943
- Acronym / sponsor ID
- NST-CA005CTIL
- Conditions
- Metastasis to Brain of Unknown Primary
- Keywords
- cell death, PET imaging, brain metastases, stereotactic radiosurgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Replaced by a global study protocol NST-CA004
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Aposense Ltd.Industry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Jul 2009 (actual)
- Study completion
- Jul 2009 (actual)
- First posted
- 13 Jun 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 a non-invasive imaging tool for the early detection of apoptosis in brain metastases in response to radiation therapy, in patients subjected to stereotactic radiosurgery (SRS). Such early detection may improve clinical management of patients with brain metastases, as it may help early identification of non-responders, and subsequently potentially lead to optimization of radiation techniques such as the need for whole brain radiation therapy (WBRT), addition of brain penetrating chemotherapy or an early decision on referral of the patient with non-responsive lesions to surgery or to systemic chemotherapy. The experimental design of the present study aims to evaluate the potential of non-invasive PET examination with [18F]-ML-10, to provide the clinician with an assessment of response early in the course of treatment, via non-invasive molecular imaging of radiation-induced apoptosis. This information on tumor responsiveness is currently available only several weeks to months after completion of radiotherapy.
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 first clinical indication for which [18F]-ML-10 is being developed is imaging of apoptosis in clinical oncology to monitor tumor response to radiation 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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 18F-ML-10, | Experimental | Drug: ([18F]-ML-10)Pre-treatment baseline and post treatment follow-up 18F ML-10 PET/CT sessions. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- The Patient may only be included in the study if ALL of the following statements are fulfilled:
- Male or female patient diagnosed with metastatic non hematological cancer, with up to 4 brain metastases of which at least one has a minimal diameter of 1.5cm , as assessed by MRI (utilized for SRS planning) and is scheduled for SRS. These metastases will be defined as target lesions.
- Patient is ≥ 18 years of age at the time of signature of the informed consent form.
- Fully conscious patient who has been given written and verbal information, and has then provided an informed consent.
- Patient who is able to cooperate with the studies requirements to lie still during PET/CT imaging scans, which may last for up to 3 hours.
Key exclusion criteria (10 listed)
- Unstable medical condition, such as severe ischemic heart disease, liver disease or pulmonary disease, which may risk the patient during the study, as judged by the investigator.
- Any indication of imminent brain herniation
- Any known psychiatric disorder other than mild depression or anxiety.
- Known allergy to Gadolinium
- Other condition that might jeopardize the safety of the patient or the evaluation of the study results, as judged by the investigator.
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 |
|---|---|---|
| ([18F]-ML-10)Also: 2-(5-fluoro-pentyl)-2-methyl-malonic-acid[18F]-ML-10 was administered as an intravenous bolus injection (in 3-10 ml sterile saline solution, containing no more than 10% ethanol by volume). The radiation dose of [18F]-ML-10 administered at each session was 300-500 MBq (8.1-13.5 mCi). | Drug | 18F-ML-10, |
Primary outcome
Assessment of the change in the uptake of [18F]-ML-10 by the target lesion(s) in response to SRS, as observed by comparing the PET/CT scans before and after SRS. Target lesion is defined as having a minimal diameter of 1.5 cm
Time frame: 3 months
2 secondary outcomes
Assessment of the relationship between the change in uptake of [18F]-ML-10 by the metastatic target lesions as observed in the PET/CT scans obtained before and after irradiation, and shrinkage of the metastatic target lesion, as assessed by MRI.
Time frame: 3 months
Evaluation of the safety of [18F]-ML-10 when administered for 3 consecutive PET/CT scans to patients with brain metastases undergoing SRS.
Time frame: one month
Results and safety
The study was stopped early (reason given: Replaced by a global study protocol NST-CA004). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2013.
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.
Yael Cohen study director
Aposense Ltd.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ([18F]-ML-10) in people with Metastasis to Brain of Unknown Primary, run by Aposense Ltd..
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 13 inclusion and 10 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: stopped early, as of the sponsor's last update on 15 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was stopped early (reason given: Replaced by a global study protocol NST-CA004). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of the change in the uptake of [18F]-ML-10 by the target lesion(s) in response to SRS, as observed by comparing the PET/CT scans before and after SRS. Target lesion is defined as having a minimal diameter of 1.5 cm (time frame: 3 months). 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 15 Feb 2013.