XCancer

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

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 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.

Sponsor:

National Institute of Diabetes and Digestive and Kidney Diseases

Phase:

Phase 1/2

Government Study Link:

NCT01176500 - Click here to see study on

ClinicalTrials.gov

Fluciclatide

Isotope(s):
Target(s):
  • αvβ3
Ligand Class: Peptides
Inclusion
  • 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 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 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 not had a biopsy of the target lesion within 7 days of PET/CT imaging.
  • * 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)
Exclusion
  • * 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 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 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.