Protocol Number: 09-C-0080

Title:

A Phase 2, Open-label, Proof-of-Concept Study to Assess the Ability to Detect Tumours and Angiogenesis via the Expression of Alpha v Beta 3 Integrin Receptors by (18F)AH-111585 PET Imaging

Number:

09-C-0080

Summary:

Background:

-Angiogenesis is the growth of new blood vessels from pre-existing blood vessels.

-Increased angiogenesis is observed in certain abnormal conditions such as tumor growth.

- AH-111585 is a small cyclic peptide containing the RGD tripeptide, which preferentially binds with high affinity to alpha(v)beta3 integrins which are upregulated in angiogenesis

- [18F]AH-11585 is a new radiotracer developed for PET imaging which targets alpha(v)beta3 receptors.

- Initial clinical studies performed in Europe demonstrate that [18F]AH-11585 is safe and well tolerated and may be useful in the evaluation of patients with certain types of tumor where angiogenesis plays a significant role.

Objectives:

Primary

-To correlate the magnitude of [18F]AH-111585 uptake and retention with quantitative measurement of the levels of alpha(v)beta3 integrin expression in tumors.

Secondary

-To correlate [18F]AH-111585 accumulation in tumors obtained from PET images to the expression of angiogenesis markers and microvessel density in tumors.

- To obtain preliminary data on the feasibility of detection of both primary and metastatic tumor lesions in using [18F]AH-111585 PET as compared to standard of care modalities.

- To assess the safety of a single IV administration of a maximum activity of 375 MBq [18F]AH-111585 in subjects with solid tumors.

Eligibility:

-Adult participants (greater than or equal to 18 years old) at initial diagnosis or recurrence with tumors greater than or equal to 2.5 cm in diameter (not within the liver) 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; renal cell carcinoma, and melanoma who are scheduled to undergo resection or biopsy of the tumor as a result of routine clinical treatment.

-The participant has a blood urea nitrogen value and serum creatinine value of less than or equal to 1.5 of the upper normal limit, platelet count of greater than 75,000 x 10(6)/L, hemoglobin value of greater than 9 g/dL, PT and an activated PTT within normal limits.

-The participant 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 and is competent to sign informed consent.

-The participant has not received any anti-angiogenic agents (e.g. bevacuzimab, sorafenib, sunitinib) within 60 days prior to PET imaging.

- The participant has had no open wounds within 10 days prior to study entry.

Exclusion Criteria:

-The participant is pregnant or lactating.

- The participant is being treated with heparin or coumadin.

- The participant 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 participant experienced substantial changes in their medical status before all essential study procedures (including all imaging procedures and surgical excision or biopsy) are performed.

- The participant has any contraindication to any of the study procedures, products used or its constituents (e.g. X-ray contrast media).

- The participant is unable to lie down for 125 minutes or the participant suffers from claustrophobia.

- The participant has known diagnosis of human immunodeficiency virus (HIV), hepatitis B or C infection.

- 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.

Design:

This will be a phase 2, open-label, proof-of-concept study to assess the ability of [18F]AH-111585 PET imaging to detect tumors and angiogenesis via the expression of alpha(v)beta3 integrin receptors. Up to 30 evaluable subjects are planned to be included at up to 4 study centers in the US. Subjects will undergo one [18F]-AH-111585 PET/CT imaging study which will be correlated (Spearman's rank or Pearson's as appropriate) with angiogenic markers and microvessel density parameters from clinically indicated biopsy or resection specimen, and standard of care diagnostic imaging parameters. Patients at NCI will NOT undergo DCE-CT, as this is only an optional study in the protocol.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

General inclusion criteria for all subjects:

Subjects may be included in the study if they meet all of the following criteria:

(1) The subject is greater than or equal to 18 years old.

(2) The subject has been diagnostically imaged and is suspected of having a primary or metastatic tumour lesion greater than or equal to 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

-Melanoma

(3) The subject is scheduled to undergo resection or biopsy of the greater than or equal to 2.5 cm target tumor as a result of routine clinical treatment.

(4) 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.

(5) 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.

(6) The subject is able and willing to comply with study procedures, and signed and dated informed consent is obtained.

(7) The subject has a blood urea nitrogen value and serum creatinine value of less than or equal to 1.5 of the upper normal limit.

(8) The subject has a platelet count of greater than 75,000 times 10(6)/L.

(9) The subject has a haemoglobin value of greater than 9 g/dL.

(10) The subject has a prothrombin time and aPTT within normal limits.

(11) 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.

(12) The subject has not received any anti-angiogenic agents (e.g. bevacuzimab, sorafenib, sunitinib) within 10 days prior to PET imaging.

(13) The subject has had no open wounds within 10 days prior to study entry.

(14) The chosen target tumor is not within the liver.

This study is designed to include women and minorities. Men and women will be recruited with no preference to gender. No exclusion from this study will be based on race.

Inclusion criteria specific for subjects with suspected or previously diagnosedhigh-grade glioma:

Subjects may be included in the study if they meet all of the criteria in Section 7.2.1 along with the following criteria:

(1) 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.

(2) 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:

Subjects must be excluded from participating in this study if they meet any of the following criteria:

(1) The subject is lactating.

(2) The subject is being treated with heparin or coumadin.

(3) The subject has received another IMP within 14 days before, or will receive an IMP within 1 week after administration of AH-111585 (18F) Injection.

(4) The subject was previously included in this study.

(5) 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.

(6) The subject has any contraindication to any of the study procedures, products used or its constituents (e.g. X-ray contrast media).

(7) 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, Haemophilia A/B/C, Factor-V Leiden, and Bernard-Soulier syndrome.

(8) The subject is unable to lie down for 125 minutes.

(9) The subject suffers from claustrophobia.

(10) The subject has known diagnosis of human immunodeficiency virus (HIV) infection.

(11) The subject has known diagnosis of hepatitis B or C infection.

(12) The subject has known diagnosis of mental incapacitation and it affects their ability to consent.

(13) The subject has a history of serious hypersensitivity reaction to iodinated contrast media.

Special Instructions:

Currently Not Provided

Keywords:

Angiogenesis

(18F) AH-111585

PET Imaging

Recruitment Keyword(s):

Lung Cancer

Kidney Cancer

Renal Cell Cancer

Head and Neck Cancer

Melanoma

Brain Cancer

Condition(s):

Lung Cancer

Renal Cell Carcinoma

Head and Neck Cancers

Melanoma

Brain Cancer

Investigational Drug(s):

[18F]AH-111585

Investigational Device(s):

None

Intervention(s):

Drug: [18F]AH-111585

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Albelda SM, Mette SA, Elder DE, Stewart R, Damjanovich L, Herlyn M, Buck CA. Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 1990 Oct 15;50(20):6757-64.

Beer AJ, Haubner R, Sarbia M, Goebel M, Luderschmidt S, Grosu AL, Schnell O, Niemeyer M, Kessler H, Wester HJ, Weber WA, Schwaiger M. Positron emission tomography using [18F]Galacto-RGD identifies the level of integrin alpha(v)beta3 expression in man. Clin Cancer Res. 2006 Jul 1;12(13):3942-9.

Bello L, Francolini M, Marthyn P, Zhang J, Carroll RS, Nikas DC, Strasser JF, Villani R, Cheresh DA, Black PM. Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery. 2001 Aug;49(2):380-9; discussion 390.

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