Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Lung Neoplasms

Carcinoma

Carcinoma, Squamous Cell

Carcinoma, Hepatocellular

Hypoxia

Carcinoma, Renal Cell

Head and Neck Neoplasms

Kidney Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neoplasms, Squamous Cell

Adenocarcinoma

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

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

Skin and Connective Tissue Diseases

Breast Neoplasms

Triple Negative Breast Neoplasms

Breast Diseases

Skin Diseases

CA IX is a transmembrane protein, it exhibits cytoplasmic membrane staining. Immunohistochemically positive cells were graded as Low staining if they constituted \<10% of the total.

CA IX is a transmembrane protein, it exhibits cytoplasmic membrane staining. Immunohistochemically positive cells were graded as high staining if they constituted ≥ 10%

CA IX is a transmembrane protein, it exhibits cytoplasmic membrane staining. Immunohistochemically positive cells were graded as Low staining if they constituted \<10% of the total and high staining if they constituted ≥ 10% (15).

Carbonic anhydrase staining levels

Triple-negative breast carcinoma is characterized by the absence of estrogen receptors, progesterone receptors, and HER2/neu receptors. Carbonic anhydrase IX (CA IX) is a tumor-associated cell surface glycoprotein that is involved in adaptation to hypoxia-induced acidosis and plays a role in cancer progression. This study aimed to investigate CA IX expression in TNBC and its relationship with treatment effect.

Tru-cut biopsy materials, sent to our hospital pathology laboratory between August 2018 and May 2023, will be examined. Invasive carcinoma cases will be evaluated according to estrogen, progesterone, and HER 2 receptor levels. Triple-negative tumor cases were isolated and those cases who underwent breast resection in our hospital after receiving neoadjuvant chemotherapy (Adriamycin, cyclophosphamide, and then paclitaxel for 4 cycles) were included in the study.

Carbonic Anhydrase IX Enzyme in Triple Negative Breast Carcinoma

Carbonic Anhydrase IX Enzyme in Triple Negative Breast Carcinoma: Relationship With Prognostic Factors and Response to Neoadjuvant Chemotherapy

Higher staining CA IX levels (≥ 10%) in TNBC patients' pathological specimens is a poor prognostic factor

Treatment success in TNBC patients by evaluating changes in CA IX staining levels

Kahramanmaras Sutcu Imam University

Professor, Associate

Signs and Symptoms, Respiratory

Hematinics

All Drugs and Chemicals

Liver Extracts

The age and gender of patients are not limited. The patient was preliminarily diagnosed as renal carcinoma by imaging examination and finally diagnosed as clear cell renal cell carcinoma by pathology.

The age and sex of the healthy control group were matched with that of ccRCC patient group. There was no tumor in the kidney or other parts of the body, and no tumor in the blood system. The healthy control group did not have any renal benign diseases, such as kidney stones, diabetic nephropathy, inflammation, and uremia. There are no inflammatory diseases in other parts of the body. The functions of the liver, kidney, and heart were normal.

The age and sex of this group were matched with that of ccRCC patient group. The patient did not have any tumor but had one of the benign kidney diseases, such as kidney stones, diabetic nephropathy, inflammation, and uremia. The functions of the liver and heart were normal.

The patient was treated normally and no intervention was required in this study

No intervention was required for patients or control group in this study

Li Zhang, Dr.

li zhang, Ph.D.

Renal cell carcinoma (RCC) is one of the common malignant tumors in human beings and originates from the renal tubular epithelium. Clear cell renal cell carcinoma (ccRCC) is the main pathological type of RCC. Due to the lack of reliable biomarkers and clinical symptoms for early diagnosis, imaging findings such as ultrasound and CT are needed. When the patients presented typical symptoms, for example, hematuria, backache, and abdominal mass, some of them are in advanced stages of cancer. About a quarter of patients had metastasis at the first diagnosis, and the 5-year survival rate of these patients was less than 10%. Therefore, the early diagnosis of ccRCC and the prevention of tumor recurrence and metastasis are of great significance.

The preliminary studies suggested that some hypoxia and metabolism-related molecules were highly expressed in ccRCC tumors but low in normal kidney tissues. The molecules included carbonic anhydrase IX/9 (CA IX/CA9), the mitochondrial NADH dehydrogenase \[ubiquinone\] 1 alpha subcomplex, 4-like 2(NDUFA4L2), angiopoietin-like protein 4(ANGPTL4), hypoxia inducible lipid droplet-associated (HILPDA）, and egl-9 family hypoxia-inducible factor 3( EGLN3) et al . Cell-free DNA methylomes were also highly expressed in the blood of ccRCC patients.

In order to further verify the expression status of the above novel biomarkers in ccRCC, the investigators will detect the expressions of these molecules in the tumor and adjacent tissues from 140 ccRCC patients by RT-PCR, Western blot, and immunohistochemistry.140 healthy people were selected as the control group. 30 patients with benign kidney diseases were selected as another control group. Blood and urine samples from the ccRCC group and the control group were collected. The mRNA and protein levels of the above molecules in blood or urine samples were detected by qRT-PCR and ELISA. The correlation between the expression of the above new biomarkers and clinical data, such as early diagnosis, pathological grade, recurrence and metastasis, and survival time, was statistically analyzed. The above molecular changes were dynamically detected before surgery, 1 week, and 6 months after surgery. A receiver-operating characteristic curve (ROC) was used to determine the threshold value of these biomarkers for the diagnosis of renal clear cell carcinoma.

The study is to explore the specific tumor biomarker spectrum for clinical diagnosis, evaluation of recurrence, metastasis, and prognosis of ccRCC, which will be auxiliary early screening and diagnosis, reducing the harm of renal cancer to human health.

Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma

There is no plan to share individual participant data (IPD) until the project is completed. Sharing IPD may be available 1 year after publication.

1. The expressions of novel biomarkers in blood samples: The protein levels of CA9, NDUFA4L2, ANGPTL4, HILPDA and EGLN3 in blood samples were detected by ELISA method. The levels of cell-free DNA methylomes in blood samples were detected by real-time fluorescence quantitative PCR method.
2. The expressions of novel biomarkers in urine samples: The levels of cell-free DNA methylomes in urine samples were detected by real-time fluorescence quantitative PCR method.

1. The expressions of novel biomarkers in tissues: In the tumor and adjacent tissues from ccRCC patients, the mRNA expressions of CA9, NDUFA4L2, ANGPTL4, HILPDA and EGLN3 were measured by real-time fluorescence quantitative PCR method. The protein expressions of these five molecules were detected by western blot, and immunohistochemistry methods.
2. The expressions of novel biomarkers in blood samples: The protein levels of CA9, NDUFA4L2, ANGPTL4, HILPDA and EGLN3 in blood samples were detected by ELISA method. The levels of cell-free DNA methylomes in blood samples were detected by real-time fluorescence quantitative PCR method.
3. The expressions of novel biomarkers in urine samples: The levels of cell-free DNA methylomes in urine samples were detected by real-time fluorescence quantitative PCR method.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
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
Carbonic Anhydrase IX Enzyme in Triple Negative Breast Carcinoma	NCT06309459	Triple Negative... Carbonic Anhydr...	Carbonic anhydr...	18 Years -	Kahramanmaras Sutcu Imam University
Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma	NCT05214885	Clear Cell Rena...	No intervention...	-	Qianfoshan Hospital
Novel Biomarkers of Hypoxia and Metabolism in Clear Cell Renal Cell Carcinoma	NCT05214885	Clear Cell Rena...	No intervention...	-	Qianfoshan Hospital

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