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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)

Phase 2
18 Years
Not Enrolling
Metastasis to Brain of Unknown Primary

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Trial Information

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)

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

Inclusion Criteria:

The Patient may only be included in the study if ALL of the following statements are

1. 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.

2. Patient is ≥ 18 years of age at the time of signature of the informed consent form.

3. Fully conscious patient who has been given written and verbal information, and has
then provided an informed consent.

4. 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.

5. ECOG performance status of 0, 1 or 2 at the time of enrollment.

6. Patient with life expectancy ≥ 12 weeks.

7. Adequate renal function and adequate hepatic function as assessed by standard
laboratory criteria and defined as:

1. Creatinine clearance ≥ 60 ml/min/1.73m2according to Cockroft & Gault Formula

2. Total bilirubin ≤ 1.5 times the ULN

3. Aspargine aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3 times the
ULN in patients without liver metastases; ≤ 5 times the ULN in patients with
liver metastases

8. Serum calcium levels, adjusted to albumin level, within normal limits.

9. For a female patient, pregnancy or breast-feeding are restricted. Woman of child
bearing potential must have a negative serum pregnancy test at screening.

Exclusion Criteria:

If any apply, the patient must not be included in the study:

1. 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

2. Any indication of imminent brain herniation

3. Any known psychiatric disorder other than mild depression or anxiety.

4. Known allergy to Gadolinium

5. Other condition that might jeopardize the safety of the patient or the evaluation of
the study results, as judged by the investigator.

6. Treatment with any non-marketed investigational drug within 30 days prior to
administration of [18F]-ML-10

7. Patient who received Whole Brain Radiation Therapy (WBRT) within 6 months prior
screening and/or planned to receive WBRT 8 weeks post SRS

8. Patient receiving concurrent treatment with temozolamide or planned to receive
temozolamide within 8 weeks post SRS

9. 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

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

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Yael Cohen

Investigator Role:

Study Director

Investigator Affiliation:

Aposense Ltd.


Israel: Israeli Health Ministry Pharmaceutical Administration

Study ID:




Start Date:

July 2008

Completion Date:

July 2009

Related Keywords:

  • Metastasis to Brain of Unknown Primary
  • cell death
  • PET imaging
  • brain metastases
  • stereotactic radiosurgery
  • Neoplasm Metastasis
  • Neoplasms, Second Primary
  • Brain Neoplasms