A Pilot, Open-label Study of 18F-Fluciclatide PET/CT Imaging in the Evaluation of Anti-angiogenic Therapy in Solid Tumors
Study Details
Study Description
Brief Summary
Background:
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Fluciclatide is a small cyclic peptide containing the RGD tri-peptide, which preferentially binds with high affinity to alpha(v)beta(3) integrins, which are up-regulated in and may regulate angiogenesis.
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[18F]Fluciclatide is a new radiopharmaceutical developed for PET imaging
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Changes in [18F]fluciclatide uptake will be evaluated before and after treatment of patients with targeted antiangiogenic drugs
Objectives:
Primary
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To determine tumor uptake and retention of [18F]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy
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Secondary
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To assess the safety of multiple intravenous (IV) administrations of Fluciclatide [18F] Injection in subjects with solid tumors
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To obtain preliminary data on the relationships between [18F]fluciclatide as a pharmacodynamic marker and standard of care imaging markers of clinical response (e.g. contrast-enhanced (CE) static computed tomography (CT), bone scintigraphy, FDG-PET), obtained as part of routine clinical follow-up as specified in the referring protocols, as well as any optional imaging performed
Eligibility:
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Patients greater than or equal to 18 years, with documented malignancy, and solid tumor greater than or equal to 1 cm outside of the liver, who are scheduled to enroll in an NCI therapy protocol using one of the anti-angiogenic agents described in the full protocol
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Platelet count greater than 75,000 x 10(6)/L, hemoglobin greater than 9g/dL, prothrombin time (PT) and aPTT less than 2 times normal limits.
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The subject has not received any targeted anti-angiogenic agents within 60 days prior to pre-treatment (baseline) [18F]fluciclatide administration
Design:
This study is intended to obtain preliminary data on the uptake and retention of [18F]fluciclatide before and after anti-angiogenic therapy. This will enable optimization of the imaging protocol, identification of the most relevant imaging parameters, and allow for calculation of the number patients required to power a larger study to assess the utility of PET imaging with [18F]fluciclatide as a pharmacodynamic biomarker in the context of targeted anti-angiogenic therapies. We expect to enroll 30 evaluable patients in this single center study. Subjects will undergo at least two [18F]fluciclatide PET/CT imaging studies, one pre-therapy and one following completion of 1 cycle of chemotherapy. An optional early post-therapy (2-7 days post therapy commencement) [18F]fluciclatide PET/CT may be performed. The magnitude of [18F]fluciclatide uptake on the pre- and post- treatment PET/CT studies will be evaluated to determine if there is a measureable difference in uptake. Data from the subject's referring therapy protocol will be reviewed for up to one year. An optional DCE-MRI scans of the target lesion may also be performed.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Detailed Description
Background:
-
Fluciclatide is a small cyclic peptide containing the RGD tri-peptide, which preferentially binds with high affinity to alpha(v)beta(3) integrins, which are up-regulated in and may regulate angiogenesis.
-
[18F]Fluciclatide is a new radiopharmaceutical developed for PET imaging
-
Changes in [18F]fluciclatide uptake will be evaluated before and after treatment of patients with targeted antiangiogenic drugs
Objectives:
Primary
-
To determine tumor uptake and retention of [18F]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy
-
Secondary
-
To assess the safety of multiple intravenous (IV) administrations of Fluciclatide [18F] Injection in subjects with solid tumors
-
To obtain preliminary data on the relationships between [18F]fluciclatide as a pharmacodynamic marker and standard of care imaging markers of clinical response (e.g. contrast-enhanced (CE) static computed tomography (CT), bone scintigraphy, FDG-PET), obtained as part of routine clinical follow-up as specified in the referring protocols, as well as any optional imaging performed
Eligibility:
-
Patients greater than or equal to 18 years, with documented malignancy, and solid tumor greater than or equal to 1 cm outside of the liver, who are scheduled to enroll in an NCI therapy protocol using one of the anti-angiogenic agents described in the full protocol
-
Platelet count greater than 150,000 x 10(6)/L, hemoglobin greater than 9g/dL, prothrombin time (PT) and aPTT less than 2 times normal limits.
-
The subject has not received any targeted anti-angiogenic agents within 60 days prior to pre-treatment (baseline) [18F]fluciclatide administration
Design:
This study is intended to obtain preliminary data on the uptake and retention of [18F]fluciclatide before and after anti-angiogenic therapy. This will enable optimization of the imaging protocol, identification of the most relevant imaging parameters, and allow for calculation of the number patients required to power a larger study to assess the utility of PET imaging with [18F]fluciclatide as a pharmacodynamic biomarker in the context of targeted anti-angiogenic therapies. We expect to enroll 30 evaluable patients in this single center study. Subjects will undergo at least two [18F]fluciclatide PET/CT imaging studies, one pre-therapy and one following completion of 1 cycle of chemotherapy. An optional early post-therapy (2-7 days post therapy commencement) [18F]fluciclatide PET/CT may be performed. The magnitude of [18F]fluciclatide uptake on the pre- and post- treatment PET/CT studies will be evaluated to determine if there is a measureable difference in uptake. Data from the subject's referring therapy protocol will be reviewed for up to one year. An optional DCE-MRI scans of the target lesion may also be performed.
Study Design
Outcome Measures
Primary Outcome Measures
- To determine tumor uptake and retention of [18F]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy. [2 years]
Secondary Outcome Measures
- To obtain preliminary data on the relationships between [18F]fluciclatide as a pharmacodynamic marker and standard of care imaging markers of clinical response. [2 years]
- To assess the safety of multiple intravenous (IV) administrations of Fluciclatide [18F] Injection in subjects with solid tumors. [2 years]
Eligibility Criteria
Criteria
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INCLUSION CRITERIA:
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Adult subjects (greater than or equal to18 years old), with documented malignancy, with at least one solid tumor greater than or equal to 1 cm in diameter (not within the liver), who are scheduled to enroll in an NCI therapy protocol using one of the anti-angiogenic therapy agents (Vandetanib, Cediranib or Bevacizumab)
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The subject has a platelet count of 150,000 x 10(6)/L, hemoglobin value of greater than 9 g/dL, PT and an aPTT less than 2 times normal limits.
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The subject has a clinically acceptable medical history, physical examination and vital signs findings during the screening period (from less than 4 weeks before administration of Fluciclatide (18F) Injection); i.e. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
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The subject has had no open surgical wounds in close proximity to the target lesion(s) within 10 days prior to study entry.
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The subject has not had a biopsy of the target lesion within 7 days of PET/CT imaging.
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The subject has not had radiation therapy to the region of the target lesion.
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Enrolling in the following NCI anti-angiogenic therapy protocols:
08-C-0020
09-C-0192
07-C-0058
09-C-0019
EXCLUSION CRITERIA:
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The subject is pregnant or lactating.
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The subject is being treated with doses of heparin or warfarin resulting in elevation of PT or aPTT greater than 2 times normal.
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The subject has received any anti-angiogenic agent (e.g. bevacizumab, sorafenib, sunitinib) within 60 days prior to pre-treatment (baseline) [18F]fluciclatide PET imaging. This stipulation does not apply after the baseline [18F]fluciclatide PET imaging.
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The subject has received another investigational medicinal product (IMP) within 24 hours before or is scheduled to receive another IMP within 24 hours after Fluciclatide (18F) Injection.
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The subject has any contraindication to any of the study procedures, products used or its constituents (e.g. severe claustrophobia unrelieved by oral anxiolytics).
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The subject is unable to lie still for 75 minutes.
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The subject is known to have a history of hyper- or hypo-coagulation syndromes resulting in prolongation of bleeding parameters. Such coagulopathies include but are not limited to Von Willebrand disease, Protein C deficiency, Protein S deficiency, Hemophilia A/B/C, Factor-V Leiden, and Bernard-Soulier syndrome.
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The subject has undergone a surgical procedure to the target lesion within 28 days prior to baseline [18F]fluciclatide administration OR is scheduled to undergo a surgical procedure between the baseline and post 1-cycle [18F]fluciclatide PET/CT.
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The subject has only bone metastasis
ADDITIONAL INCLUSION CRITERIA FOR SUBJECTS UNDERGOING OPTIONAL MR:
-Serum creatinine within 2 weeks prior to MRI less than or equal to 1.8mg/dl and estimated glomerular filtration rate (eGFR) must be greater than 30 ml/min/1.73m(2).
ADDITIONAL EXCLUSION CRITERIA FOR SUBJECTS UNDERGOING OPTIONAL MR:
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The subject has known allergy to gadolinium
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The subject has contraindications to MRI:
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Subjects must weigh less than 136 kg (weight limit for scanner table).
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Subjects cannot have pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with MRI.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
- National Institutes of Health Clinical Center (CC)
- GE Healthcare
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569-71.
- Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002 Mar;2(3):161-74. Review.
- Line BR, Mitra A, Nan A, Ghandehari H. Targeting tumor angiogenesis: comparison of peptide and polymer-peptide conjugates. J Nucl Med. 2005 Sep;46(9):1552-60.
- 100173
- 10-C-0173