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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.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00805636
Recruitment Status : Unknown
Verified April 2010 by Aposense Ltd..
Recruitment status was:  Recruiting
First Posted : December 9, 2008
Last Update Posted : May 12, 2010
Information provided by:
Aposense Ltd.

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.

Condition or disease Intervention/treatment Phase
Brain Metastases Solid Tumors Drug: 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([18F]-ML-10) Radiation: Stereotactic Radio-Surgery (SRS) therapy Procedure: Positron Emission Tomography Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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 Start Date : November 2008
Estimated Primary Completion Date : October 2010
Estimated Study Completion Date : October 2010

Resource links provided by the National Library of Medicine

Intervention Details:
  • Drug: 2-(5-fluoro-pentyl)-2-methyl-malonic-acid ([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).
    Other Name: [18F]-ML-10
  • Radiation: Stereotactic Radio-Surgery (SRS) therapy
    SRS will be administered according to the standard of care using a radiation dose of 14-24 Gy to each lesion.
  • Procedure: Positron Emission Tomography
    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.

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. To perform additional analyses for all other lesions with longest diameter ≥ 1.5 cm treated by SRS. [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00805636

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United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Juho Whang   
Principal Investigator: Eric Wong, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Elysia Larson       ELARSON@LROC.HARVARD.EDU   
Principal Investigator: Stephanie E Weiss, MD         
United States, New York
Department of Radiation oncology, Memorial Sloan Kettering Cancer Center Recruiting
New York city, New York, United States, 10065
Contact: Gina Giannantoni-ibelli   
Principal Investigator: Kathryn Beal, MD         
United States, Pennsylvania
UPMC Shadyside Radiation Oncology Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Rhonda Berlin   
Principal Investigator: Heron Dwight, MD         
Sponsors and Collaborators
Aposense Ltd.
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Responsible Party: Miri Ben-Ami, MD, Aposense Identifier: NCT00805636    
Other Study ID Numbers: NST-CA004CTIL
First Posted: December 9, 2008    Key Record Dates
Last Update Posted: May 12, 2010
Last Verified: April 2010
Keywords provided by Aposense Ltd.:
cell death
PET imaging
brain metastases
stereotactic radiosurgery
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplasms, Second Primary
Brain Neoplasms
Neoplastic Processes
Pathologic Processes
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases