A Pilot, Open-label Study of 18F-Fluciclatide PET/CT Imaging in the Evaluation of Anti-angiogenic Therapy in Solid Tumors

Study Overview
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Brief Summary
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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 75,000 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.

Detailed Description
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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.

Official Title
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A Pilot, Open-Label, Proof-of-Concept Study of the Use of [18F]Fluciclatide PET/CT Imaging in the Evaluation of Anti-Angiogenic Therapy in Solid Tumors

Conditions
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Colon Cancer, Lung Cancer, Cervical Cancer, Renal Cell Carcinoma, Uterine Cancer

Intervention / Treatment
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* Drug: (18)Fluciclatide


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: 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) 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. 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. The subject has had no open surgical wounds in close proximity to the target lesion(s) within 10 days prior to study entry. The subject has not had a biopsy of the target lesion within 7 days of PET/CT imaging. The subject has not had radiation therapy to the region of the target lesion. Enrolling in the following NCI anti-angiogenic therapy protocols: 08-C-0020 09-C-0192 07-C-0058 09-C-0019 EXCLUSION CRITERIA: The subject is pregnant or lactating. The subject is being treated with doses of heparin or warfarin resulting in elevation of PT or aPTT greater than 2 times normal. 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. 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. The subject has any contraindication to any of the study procedures, products used or its constituents (e.g. severe claustrophobia unrelieved by oral anxiolytics). The subject is unable to lie still for 75 minutes. 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. 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. 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: The subject has known allergy to gadolinium The subject has contraindications to MRI: Subjects must weigh less than 136 kg (weight limit for scanner table). Subjects cannot have pacemakers, cerebral aneurysm clips, shrapnel injury, or other implanted electronic devices or metal not compatible with MRI.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: (18)Fluciclatide|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PET Imaging, (18F)Fluciclatide, Anti-Angiogenic Therapies, Solid Tumors