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

NCT01176500 | Withdrawn Phase 1

• 2 other identifiers: 10017310-C-0173
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Colon Cancer; Lung Cancer; Cervical Cancer; Renal Cell Carcinoma; Uterine Cancer

Keywords

PET Imaging; (18F)Fluciclatide; Anti-Angiogenic Therapies; Solid Tumors

Outcome Measures

Primary Outcomes (1)

• To determine tumor uptake and retention of [18F]fluciclatide before and after 1 cycle of treatment with targeted anti-angiogenic therapy.

  2 years

Secondary Outcomes (2)

• 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

Interventions

(18)Fluciclatide DRUG

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• C-0020
• C-0192
• C-0058
• C-0019

You may not qualify if:

• 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
• 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).
• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• National Institutes of Health Clinical Center (CC): collaborator
• GE Healthcare: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Brooks PC, Clark RA, Cheresh DA. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 1994 Apr 22;264(5158):569-71. doi: 10.1126/science.7512751.

  PMID: 7512751 BACKGROUND

• 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.

  PMID: 16157540 BACKGROUND

• Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002 Mar;2(3):161-74. doi: 10.1038/nrc745.

  PMID: 11990853 BACKGROUND

MeSH Terms

Conditions

Colonic Neoplasms; Lung Neoplasms; Uterine Cervical Neoplasms; Carcinoma, Renal Cell; Uterine Neoplasms

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: August 5, 2010
• First Posted: August 6, 2010
• Study Start: July 28, 2010
• Primary Completion: November 18, 2011
• Study Completion: November 18, 2011
• Last Updated: July 2, 2017

Record last verified: 2011-11-18

Locations

US (1)