Clinical trial NCT00805636: 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.
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Brain Metastases
Solid Tumors
Keywords: cell death
PET imaging
brain metastases
stereotactic radiosurgery
Lead sponsor: Aposense Ltd.
Sponsor class: INDUSTRY
First posted: 2008-12-09
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. ECOG performance status of 0, 1 or 2 at the time of enrollment.
3. Women of child-bearing potential must have a negative blood pregnancy test at screening and use an adequate and medically acceptable contraceptive method.
4. Willing and able to follow the protocol requirements.
5. Able to provide written informed consent.

Exclusion Criteria:

1. 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.
2. Any indication of a risk for an imminent brain herniation, as evaluated by the Principal Investigator, based on the findings on brain MRI.
3. Treatment with whole brain radiation therapy (WBRT) within 3 months prior to screening.
4. Evidence for hemorrhage within any of the brain metastases.
5. Any known psychiatric disorder other than mild depression or anxiety that may affect adherence to the study requirements.
6. Known allergy to gadolinium.
7. Any contraindication to MR imaging (e.g., metal implant, aneurysm clip, pacemaker).
8. Other condition that, in the opinion of the Investigator, might jeopardize the safety of the patient, or the adequate evaluation of study results.
9. Treatment with any investigational drug, device or biologic agent within 30 days prior to administration of \[18F\]-ML-10.

Primary outcomes:
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
timeFrame: 1 year
Secondary outcomes:
measure: 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
timeFrame: 1 year
measure: 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)
timeFrame: 1 year
measure: To perform additional analyses for all other lesions with longest diameter ≥ 1.5 cm treated by SRS.
timeFrame: 1 year
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: New York city
country: United States
facility: Department of Radiation oncology, Memorial Sloan Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: UPMC Shadyside Radiation Oncology
state: Pennsylvania
Study officials:
References: