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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

All Drugs and Chemicals

Immunomodulating Agents

Immunologic Factors

The registered patients will received CAR-T cell immunotherapy for the new specific chimeric antigen receptor of CAIX antigen by infusion.

This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at CAIX antigen.

CAR-T cell immunotherapy

Hailong Li, M.D/Ph.D

Qing Zhang, Ph.D

Junnian Zheng, M.D/Ph.D

This is an experimental study to evaluate the safety and efficacy of CAR T cells targeting CAIX in the treatment of advanced renal cancer.

We designed a clinical study and divided the trial into two phases.

Phase 1 (climbing test) : 12 patients were randomly divided into 4 groups (n=3). 12 patients were treated with cyclophosphamide at the dose of 60mg/kg/d 8-7 days before CAR-T cell infusion, and fludalabine at the dose of 25mg/m\^2/d 6-2 days before CAR-T cell infusion. 5 mg anti-human CAIX monoclonal antibody (G250) was injected into the hepatic artery of each patient by an interventional catheter on the day before CAR-T cells infusion. On Day 0, CAR T cells were injected into patients in group 1, 2, 3 or 4 at the dose of 1x10\^7/ person, 1\*10\^8/ person, 1\*10\^9/ person or 1\*10\^10/ person, respectively. The infusion time is about 15-30min. On day 0-14, IL-2 (75000IU/kg) was injected subcutaneously once a day. From day 15-28, IL-2 (75000IU/kg) was subcutaneously injected into the patients three times a week. The purpose of this study is to assess subjects' MTD (maximum tolerated dose) against CAR T cells.

Phase 2: After determining the appropriate therapeutic dose for patients with renal cell carcinoma, 8 patients received the same pre-treatment of chemotherapy and G250 antibody. Then, the appropriate therapeutic dose of CAR T cells according to the results of phase 1 was infused on Day 0. On day 0-14,IL-2 (75000IU/kg) was given subcutaneously once a day. On day 15-28, IL-2 (75000IU/kg) was given subcutaneously three times a week.

Peripheral blood was collected every 4 weeks to evaluate proliferation and survival of CAR-T cells. After 6 months of close follow-up, subjects will undergo a medical history evaluation, physical examination, and blood tests quarterly for 2 years. After this assessment, subjects will be enrolled in an annual telephone follow-up and questionnaire study for up to five years to evaluate treatment for long-term health problems, such as recurrence of malignant tumors.

Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma

To evaluate the incidence and severity of possible adverse events within one month after targeted CAIX CAR-T infusion, including cytokine release syndrome and on-target toxicity.

In order to observe the efficacy of CAR-T cells after infusion, total remission rate (ORR), complete remission (CR), partial remission (PR), disease stability (SD) or progression (PD) will be used for evaluation.

Xuzhou Medical University

The Affiliated Hospital of Xuzhou Medical University

Peposertib

Protein Kinase Inhibitors

Enzyme Inhibitors

Diagnostic test: A single IV administration of 37 Megabecquerel (+/- 10%) 89Zr-DFO-girentuximab, containing a mass dose of 10 mg of girentuximab, followed by a diagnostic scan

Treatment test: A single IV administration that could be 1887 - 2516 or 3145 Megabecquerel (+/- 10%) 177Lu-DOTA-girentuximab,containing a mass dose of 10 mg of girentuximab, on Day 1 of each 84-day cycle and p.o. administration of that could be 100-150 or 200 mg Peposertib BID on days 4-21 of each 84-day cycle.

Single IV administration followed by 89Zr-DFO-girentuximab PET/CT (or PET/MRI) scan at screening and approximately 8-10 weeks (±1 week) after Cycle 3 Day 1, as well as at the end of treatment visit (if feasible). The PET/CT should be obtained within 4-7 days after 89Zr-TLX250 administration

89Zr-TLX250

Dose escalation and de-escalation for the determination of the Maximum tolerated combination/ Recommended phase 2 dose.

All subjects will receive 177Lu-TLX250 intravenously on day 1 and Peposertib BID on days 4-21 of each 84-day cycle.

177Lu-TLX250 and Peposertib

MEDICAL DIRECTOR, MD

Principal Investigator

Howard Gurney

Dainik Patel

Kenneth O'Byrne

Princiapl Investigator

Andrew Scott

Nat Lenzo

This is an open label, single-arm, multicentre dose escalation (Part 1) and dose expansion (Part 2) study to evaluate different combinations of 3 radioactive dose levels of 177Lu-TLX250 administered intravenously with 3 different doses of peposertib in patients with CAIX-expressing solid tumors.

Part 1 (dose escalation) will evaluate the combination of 3 different activities of 177Lu-TLX250 and 3 different dose levels of peposertib.

Patients with CAIX positive solid tumors will be enrolled in a given dose/activity level in Cohorts of approximately 2-6 patients.

Treatment cycles will have a fixed length of 84 days. Patients will be treated during 3 cycles, or until clinically significant progression or unacceptable toxicity.

Part 2 (dose expansion) patients will be enrolled in 2 Cohorts:

* Cohort A: 40 patients with metastatic or non-resectable ccRCC
* Cohort B: 20 patients with CAIX-positive solid tumors (excluding RCC).

Patients will be treated at the Recommended phase 2 dose of 177Lu-TLX250 in combination with peposertib at the dosing schedule of the selected Recommended phase 2 dose.

Dose escalation/de-escalations will be supported by the guidance given by outputs of the Bayesian model-based dose-escalation design.

Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors

A Phase 1b Dose Escalation/Expansion Study of the Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX (CAIX)-Expressing Solid Tumors

Dose level toxicity evaluation using Partial Ordering Bayesian Logistic Regression Model Method (PO-BLRM)

Frequency of occurrence and severity of abnormal findings in safety investigations regarding Laboratory examinations

Frequency of occurrence and severity of abnormal findings in safety investigations regarding the vital signs

Frequency of occurrence and severity of abnormal findings in the 12-lead ECG (ECG QT interval)

Assessment of AEs graded by the Common Terminology Criteria for Adverse Events (CTCAE) Criteria, Version 5.0

Quality of life ( in terms of their ability to care for themself, daily activity, and physical ability (walking, working) is to be evaluated using the ECOG Performance Scale.

Overall Survival (OS), determined from enrollment , until death from any cause

Tumor response in terms of objective response rate (ORR) (solid tumor tissue response and overall radiological response \[tumor response by RECIST 1.1 and overall radiological response by RECIST 1.1\])

Progression free survival (PFS) defined as the time from enrollment to disease progression confirmed by radiology, clinical progression or death (whichever comes first)

This outcome will be measured by analyzing the incidence of ADA(HACA) formation in blood on day 1, day 22, Day 43, Day 57 of each cycle (each cycle is 84 days) and at the end of treatment visit.

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
Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma	NCT04969354	Immunotherapy	CAR-T cell immu...	18 Years - 70 Years	The Affiliated Hospital of Xuzhou Medical University
Clinical Study of CAIX-targeted CAR-T Cells in the Treatment of Advanced Renal Cell Carcinoma	NCT04969354	Immunotherapy	CAR-T cell immu...	18 Years - 70 Years	The Affiliated Hospital of Xuzhou Medical University
Combination of 177Lu-TLX250 and Peposertib in Patients With Carbonic Anhydrase IX -Expressing Solid Tumors	NCT05868174	Solid Tumor, Ad... Advanced Solid ... Advanced Renal ...	89Zr-TLX250 177Lu-TLX250 an...	18 Years -	Telix Pharmaceuticals (Innovations) Pty Limited

Spots Global Cancer Trial Database for caix

Every month we try and update this database with for caix cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for caix

Every month we try and update this database with for caix cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for caix cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.