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.
|ClinicalTrials.gov 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
|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|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
- 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.
- 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 ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00805636
|United States, Massachusetts|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02115|
|Contact: Juho Whang email@example.com|
|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 GiannanG@mskcc.org|
|Principal Investigator: Kathryn Beal, MD|
|United States, Pennsylvania|
|UPMC Shadyside Radiation Oncology||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15232|
|Contact: Rhonda Berlin berlinrL@upmc.edu|
|Principal Investigator: Heron Dwight, MD|