A Proof-of-concept Study to Assess the Ability of [18F]AH-111585 PET Imaging to Detect Tumours and Angiogenesis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GE Healthcare
ClinicalTrials.gov Identifier:
NCT00565721
First received: November 28, 2007
Last updated: February 8, 2013
Last verified: February 2013
  Purpose

This proof-of-concept study is designed to assess the ability of [18F]AH-111585 PET imaging to detect tumors and angiogenesis. Up to 30 evaluable subjects are planned to be included at up to 2 study centers in the US. Subjects are considered evaluable if they undergo administration of AH-111585 (18F) Injection, dynamic and static PET imaging, and tumor tissue acquisition. The targeted population is adult subjects at initial diagnosis or recurrence with tumors ≥2.5 cm in diameter who are scheduled to undergo resection or biopsy of the tumor as a result of routine clinical treatment. The tumors must belong to one of the following 5 types:

  • High-grade glioma, including glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma
  • Lung cancer, including small cell lung cancer and non-small cell lung cancer
  • Head and neck (H&N) tumors, including laryngeal squamous cell carcinoma, well-differentiated thyroid and oral cavity carcinoma
  • Sarcoma
  • Melanoma

Safety will be assessed from the rates of adverse events, changes in vital signs, changes in electrocardiogram (ECG) parameters, changes in physical examination findings, and changes in clinical laboratory findings.

Efficacy will be assessed as the correlations between parameters derived from the PET images and the reference standards. The reference standards will be immunohistology for αvβ3 integrins and other biomarkers specific for oncology and angiogenesis and from the standard of care imaging.

Measures obtained from optional DCE-CT imaging may also be used to compare the uptake and retention of [18F]AH-111585 in tumors obtained from the dynamic PET to assess functional status of the vascular system of the tumor.


Condition Intervention
High-grade Glioma
Lung Cancer
Head & Neck Cancer
Sarcoma
Melanoma
Drug: [18F]AH-111585

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: A Phase 2, Open-label, Proof-of-concept Study to Assess the Ability to Detect Tumours and Angiogenesis Via the Expression of ανβ3/5 Integrin Receptors by [18F]AH-111585 PET Imaging

Resource links provided by NLM:


Further study details as provided by GE Healthcare:

Primary Outcome Measures:
  • To correlate the magnitude of [18F]AH-111585 uptake and retention with quantitative measurement of the levels of ανβ3 integrin expression in tumours. [ Time Frame: Dynamic PET & Static PET immediately after administration of agent in succession; Tissue sample acquisition within 2 weeks of PET imaging. IHC of ανβ3 integrin in an ongoing manner upon receipt at TMD. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To correlate tumour perfusion and vascular permeability in tumour tissue (as measured by dynamic contrast enhanced computed tomography [DCE-CT]) with the magnitude of uptake and retention of [18F]AH-111585. [ Time Frame: Tissue sample acquisition within 2 weeks of PET imaging IHC of Oncology & angiogenic biomarkers in an ongoing manner upon receipt at TMD. DCE-CT within 2 weeks of PET and prior to tissue sample. ] [ Designated as safety issue: No ]
  • To correlate [18F]AH-111585 accumulation in tumours obtained from PET images to the expression of VEGF; VEGFr; AKT and p-AKT; MAPK and p-MAPK; and MVD in tumours by means of immunohistologic analysis of tumour tissue samples. [ Time Frame: Tissue sample acquisition within 2 weeks of PET imaging IHC of Oncology & angiogenic biomarkers in an ongoing manner upon receipt at TMD. ] [ Designated as safety issue: No ]
  • To obtain preliminary data on the feasibility of detection of both primary and metastatic tumour lesions in particular tumour types using [18F]AH-111585 PET as compared to standard of care modalities. [ Time Frame: Dynamic PET & Static PET immediately after administration of agent in succession ] [ Designated as safety issue: No ]
  • To assess the safety of a single intravenous administration of a maximum activity of 375 MBq [18F]AH-111585 in subjects with solid tumours. [ Time Frame: All blood samples at assigned time-points throughout the schedule of events. Serum samples at baseline, + 3 weeks and +6 weeks from PET imaging. ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples Without DNA

Fresh Frozen and paraffin embedded sectioned samples from resected or biopsied tumor tissue in slide format; whole blood samples; separated serum samples


Enrollment: 33
Study Start Date: November 2007
Study Completion Date: September 2012
Primary Completion Date: October 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: [18F]AH-111585
    18F labelled Cyclic RGD peptide PET agent for injection.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

The targeted subject population is adult subjects at initial diagnosis or recurrence with tumours ≥2.5 cm in diameter who are scheduled to undergo resection or biopsy of the tumour as a result of routine clinical treatment.

Criteria

Selection of Subjects: The targeted subject population is adult subjects at initial diagnosis or recurrence with tumours ≥2.5 cm in diameter who are scheduled to undergo resection or biopsy of the tumour as a result of routine clinical treatment.

General Inclusion Criteria for all Subjects:

  • The subject is ≥18 years old.
  • The subject has been diagnostically imaged and is suspected of having a primary or metastatic tumour lesion ≥2.5 cm of one of the following types: high-grade glioma, including glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma; lung cancer, including small cell lung cancer and non-small cell lung cancer; H&N tumours, including laryngeal squamous cell carcinoma, and well-differentiated thyroid and oral cavity carcinoma; sarcoma; and melanoma.
  • The subject is scheduled to undergo resection or biopsy of the ≥2.5 cm target tumour as a result of routine clinical treatment.
  • The subject is scheduled to undergo or has received standard of care diagnostic imaging work-up (following the study centre's routine procedures), e.g. CT with or without contrast, MRI with or without contrast, bone scintigraphy, X-ray, or FDG-PET.
  • Female subjects need to be either surgically sterile (has had a documented bilateral oophorectomy and/or documented hysterectomy), post menopausal (cessation of menses for more than 1 year), or if of childbearing potential the results of a serum pregnancy test performed within 24 hours must be negative and with the result known before administration of AH-111585 (18F) Injection. Female subjects of reproductive potential should also employ an effective method of birth control. Barrier contraceptives must be used throughout the study in both sexes.
  • The subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained.
  • The subject has a blood urea nitrogen value and serum creatinine value of ≤1.5 of the upper normal limit.
  • The subject has a platelet count of >75,000 x 10^6/L.
  • The subject has a haemoglobin value of >9 g/dL.
  • The subject has a prothrombin time and an activated partial thromboplastin time and within normal limits.
  • The subject has a clinically acceptable (as judged by the investigator) physical examination at screening and is capable of self-care, i.e. Eastern Cooperative Oncology Group performance status is 0 to 2, such that the subject has a high chance to complete the study.
  • The subject has not received any anti-angiogenic agents (e.g. bevacuzimab, sorafenib, sunitinib) within 10 days prior to PET imaging.
  • The subject has had no open wounds within 10 days prior to study entry.
  • The chosen target tumour is not within the liver.

Inclusion Criteria Specific for Subjects with High-grade Glioma:

  • The subject is suspected of having supratentorial malignant primary glioma (by biopsy or presenting MRI characteristics as determined by the subject's clinician) requiring further surgical resection as part of the recommended treatment plan for their newly diagnosed disease. These gliomas include glioblastoma multiforme, anaplastic astrocytoma, and anaplastic oligodendroglioma.
  • The subject has undergone recent biopsy of newly diagnosed high-grade glioma, has recovered from the effects of surgical biopsy, and baseline on-study MRI/CT is performed within 14 days of entry into the study.

Exclusion Criteria:

  • The subject is lactating.
  • The subject is being treated with heparin or coumadin.
  • The subject has received another investigational medicinal product (IMP) within 14 days before, or will receive an IMP within 1 week after administration of AH-111585 (18F) Injection.
  • The subject was previously included in this study.
  • The subject experienced substantial changes in their medical status before all essential study procedures (including all imaging procedures and surgical excision or biopsy) are performed.
  • The subject has any contraindication to any of the study procedures, products used or its constituents (e.g. X-ray contrast media).
  • The subject has known hyper- or hypo-coagulation syndromes. 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 is unable to lie down for 125 minutes.
  • The subject suffers from claustrophobia.
  • The subject has known diagnosis of human immunodeficiency virus (HIV) infection.
  • The subject has known diagnosis of hepatitis B or C infection.
  • The subject has known diagnosis of mental incapacitation and it affects their ability to consent.
  • The subject has been diagnosed with a primary or metastatic tumour lesion <2.5 cm.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565721

Locations
United States, New Jersey
GE Healthcare Office
Princeton, New Jersey, United States, 08540
Sponsors and Collaborators
GE Healthcare
Investigators
Study Director: Jeffrey Winick, Ph.D. GE Healthcare
  More Information

No publications provided

Responsible Party: GE Healthcare
ClinicalTrials.gov Identifier: NCT00565721     History of Changes
Obsolete Identifiers: NCT00923767
Other Study ID Numbers: GE-135-003
Study First Received: November 28, 2007
Last Updated: February 8, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GE Healthcare:
Static PET imaging
Dynamic PET imaging
Angiogenesis
αvβ3 integrins
oncology imaging

Additional relevant MeSH terms:
Glioma
Lung Neoplasms
Melanoma
Head and Neck Neoplasms
Sarcoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Nevi and Melanomas
Neoplasms, Connective and Soft Tissue

ClinicalTrials.gov processed this record on July 23, 2014