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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborators:
GE Healthcare
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT01176500
First received: August 5, 2010
Last updated: March 8, 2012
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Colon Cancer
Lung Cancer
Cervical Cancer
Renal Cell Carcinoma
Uterine Cancer
Drug: (18)Fluciclatide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To determine tumor uptake and retention of [18F]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

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. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To assess the safety of multiple intravenous (IV) administrations of Fluciclatide [18F] Injection in subjects with solid tumors. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: July 2010
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: (18)Fluciclatide
    N/A
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01176500

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
GE Healthcare
  More Information

Publications:
Responsible Party: Karen A. Kurdziel, M.D./NIH Clinical Center, National Institutes of Health
ClinicalTrials.gov Identifier: NCT01176500     History of Changes
Other Study ID Numbers: 100173, 10-C-0173
Study First Received: August 5, 2010
Last Updated: March 8, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
PET Imaging
(18F)Fluciclatide
Anti-Angiogenic Therapies
Solid Tumors

Additional relevant MeSH terms:
Carcinoma
Colonic Neoplasms
Carcinoma, Renal Cell
Uterine Cervical Neoplasms
Lung Neoplasms
Uterine Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Genital Neoplasms, Female
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on April 17, 2014