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Hypoxia

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Neoplasms by Histologic Type

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Liver Neoplasms

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Liver Diseases

Renal Cell Carcinoma

Clear Cell Renal Cell Carcinoma

Approximately sixteen (16) adult subjects including four (4) healthy volunteers and twelve (12) cancer subjects who have confirmed or highly suspected diagnosis of head \& neck, lung, large solitary hepatic and renal cell cancer, as defined by protocol criteria

The individual doses of \[F-18\]VM4-037 contain a maximum of 20 mCi for normal volunteers and 10 mCi for cancer subjects.

The single IP dose is administered to the study subject immediately prior to the start of PET imaging.

[F-18] VM4-037

Michael Yu, MD

Phase: Exploratory Study

Objectives: To collect drug bio-distribution data, begin collection of baseline and tumor/background imaging data, acquire experience to improve study design and the conduct of future studies

Design: Exploratory, open label, nonrandomized, multi-center study

Duration: Three visits - one screening, one imaging, and one follow-up visit at 24 hours post-dose

Procedures: Informed consent, collection of demographic information and medical history, physical examinations, vital signs, 12-lead ECGs, routine blood tests to assess major organ functions, complete blood counts and clinical chemistries for safety, blood sample for CA-IX assay, pre-dose and post-dose blood samples for metabolite analysis, dosing with \[F-18\]VM4-037, PET imaging scan, dosimetry estimation (normals), urine collections (normals), tumor immunohistochemistry with CA-IX biomarker, follow up to imaging to collect adverse events

Subjects: Approximately sixteen (16) adult subjects including four (4) healthy volunteers and twelve (12) cancer subjects who have confirmed or highly suspected diagnosis of head \& neck, lung, large solitary hepatic and renal cell cancer, as defined by protocol criteria

\[F-18\]VM4-037 is being developed as a diagnostic radiopharmaceutical for PET imaging.

SMI is seeking to determine if \[F-18\]VM4-037 might be useful as a PET ligand for the in vivo imaging of CA-IX levels in human tissue.

CA-IX is a very active enzyme which may acidify the extracellular microenvironment of tumor cells in response to hypoxia. Its expression usually promotes tumor growth and invasion, and thus impairs prognosis.

VM4-037 presents no known risks from either in vitro study in cell lines or in vivo study in animals according to in-house preclinical investigations of this compound.

The population to be studied consists of a total of approximately sixteen (16) adult subjects, which includes four normal, healthy volunteers and twelve cancer subjects with a confirmed or highly suspected diagnosis of head and neck cancer, non-small cell lung cancer, large solitary hepatic carcinoma, and renal cell carcinoma as defined by the protocol criteria.

This initial trial will be an Exploratory, Phase 0 study designed to evaluate biodistribution, collect baseline and tumor/background imaging data, and gather preliminary safety data for this investigational product. The study results will be analyzed and considered in the design of future clinical trials.

The primary objectives of this exploratory study are:

* To gain information on the bio-distribution of \[F-18\]VM4-037, to evaluate the PET images of \[F-18\]VM4-037 for resolution and signal to background ratio for tumors, and to determine CA-IX expression in tumor tissues by CA-IX antibody with immunohistochemistry
* To collect safety data, and to use this eIND in order to obtain the necessary information to file an IND (Investigational New Drug) application with the FDA (Food and Drug Administration)

The secondary objectives for this exploratory study are:

* To begin collection of baseline imaging and metabolism data
* To gain information to improve study design for the conduct of future trials

The trial is expected to begin subject enrolment in approximately April, 2009 and end subject participation in approximately September, 2009, depending on the rate of enrollment.

The subject is expected to attend three visits, adding up to several hours.

The Investigational Product (IP) being tested in this study is \[F-18\]VM4-037. The \[F-18\]VM4-037 will be administered to each qualified subject via a bolus intravenous (IV) injection. For normal volunteers, the dose will not exceed 20 mCi, as the imaging time for dosimetry is a minimum of four hours. For cancer subjects, the dose will be closer to 10 mCi (total imaging time for cancer subjects is about 2 hours).

The procedures for this study include the following:

Obtain Informed Consent, Assign Study Subject Number, Obtain Medical History, Perform Eligibility Blood Labs, Take Pre-Dose Blood Sample for CA-IX Test, Perform Pre-Dose ECG, Monitor and Collect Adverse Events, Collect Concomitant Medications, Perform Pre-Dose Physical Exam, Perform Pre-Dose ECG, Insert IV Line, Take Pre-Dose CBC and Chemistry Blood Labs, Take Pre-Dose Blood Sample for Metabolite Analysis (if applicable), Take Pregnancy Test (if applicable), Take Pre-Dose Vital Signs, Prepare and Administer IP, Perform \[F-18\]VM4-037 PET Imaging, Take Post-Dose Blood Samples for Metabolite Analysis (if applicable), Take Post-Dose Vital Signs, Perform Post-dose ECGs, Collect Urine Sample and Count for Dosimetry (normal only), Monitor Adverse Events, Collect Concomitant Medications, Perform Physical Exam 24 hr Post-Dose, Take Blood Sample for CBC and Chemistry Labs 24 hr Post-Dose, Perform ECG 24 hr Post-Dose, Take Vital Signs 24 hr Post-Dose, Monitor and Collect Adverse Events, Collect Concomitant Medications, \[F-18\]FDG PET Imaging, Immunohistochemistry

An Exploratory, Open Label, Multi-Center, Non-Randomized Study of [F-18]VM4-037

Siemens Molecular Imaging

Kirsten Saboe, Clinical Trials Monitor, Clinical Development

Signs and Symptoms, Respiratory

Administration of a single dose of the hypoxia marker Pimonidazole

Single oral dose of pimonidazole 500 mg/m2

Hypoxia marker

Navita Somaiah

The purpose of this study is to test the potential of a relatively simple serum assay that aims to identify patient subpopulations whose curative radiotherapy outcome is likely to be compromised by radiobiological tumour hypoxia (prognostic value) and who are most likely to gain (predictive value) from the addition of radiation sensitiser drugs or targeted radiotherapy dose escalation.

Aim: To analyse tiny cancer cell fragments called extracellular vesicles isolated from blood samples for their ability to identify patients with tumours that are relatively oxygen-starved and expected to be resistant to ionising radiation and many chemotherapy drugs.

Participants: 16 patients with proven cancer plus 4 healthy volunteers who give written informed consent to participate will be included in the study.

Recruitment: Eligible patients will be identified in the Outpatient Department at The Royal Marsden in Sutton or London and given a copy of the Information Sheet describing the study in detail. Dr Somaiah's team will call these potential volunteers at least 24 hours after they have received written information about the study to answer any questions. The same consent process will be followed for staff members who agree to participate as healthy volunteers. Research subjects who offer verbal agreement to participate will be asked for written consent and will be allocated a study ID. This will be used on all trial documentation and blood samples together with their initials and date of data/sample collection.

Pimonidazole administration: This well-established drug has the valuable property of binding exclusively to oxygen- starved tissues in a form that can be detected as a colour change in cell fragments released into the blood stream. A single oral dose of pimonidazole 500 mg/m2 will be prescribed and administered in a Royal Marsden outpatient clinic after confirmation of eligibility and completion of written informed consent. A member of the research team will monitor subjects to ensure that the prescribed drug is successfully taken (swallowed with water) before leaving the hospital (or going back to work/home in the case of healthy volunteers).

Blood sample: A peripheral venous blood sample of 20 ml will be collected from each participant the day after administration of pimonidazole, since it takes several hours for the drug to be absorbed and to bind to proteins and other molecules in oxygen-starved cells. A second sample will be collected 14 ±5 days later in order to confirm that all coloured cell fragments have disappeared from the circulation.

Pimo Study: Extracellular Vesicle-based Liquid Biopsy to Detect Hypoxia in Tumours

Number of cancer patients with detectable pimonidazole staining in extracellular vesicles isolated from blood samples after a single dose of pimonidazole

Institute of Cancer Research, United Kingdom

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
An Exploratory, Open Label, Multi-Center, Non-Randomized Study of [F-18]VM4-037	NCT00884520	Lung Cancer Squamous Cell C... Head and Neck C... Hepatic Carcino... Renal Cell Carc...	[F-18] VM4-037	18 Years -	Siemens Molecular Imaging
Pimo Study: Extracellular Vesicle-based Liquid Biopsy to Detect Hypoxia in Tumours	NCT03262311	Cancer	Hypoxia marker	18 Years -	Institute of Cancer Research, United Kingdom

Spots Global Cancer Trial Database for hypoxia marker