Cervical Cancer, Colon Cancer, Lung Cancer, Renal Cell Carcinoma, Uterine Cancer
Conditions
Keywords
PET Imaging, (18F)Fluciclatide, Anti-Angiogenic Therapies, Solid Tumors
Brief summary
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
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.
Interventions
DRUG(18)Fluciclatide
Sponsors
National Institutes of Health Clinical Center (CC)
GE Healthcare
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* 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
Design outcomes
Primary
| Measure | 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
| Measure | 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 |
Countries
United States
Outcome results
None listed