Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Gallium 68 PSMA-11

Immunoglobulins

Chelating Agents

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 8mg of unlabelled TLX592 (mass dose of 10mg).

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 18mg of unlabelled TLX592 (mass dose of 20mg).

Based on the result of Groups 1-3, the optimal dose and imaging timepoints will be selected to treat 3 patients with higher tumour burden (≥10 metastatic sites and/or visceral disease as detected on a 68Ga-PSMA-11 or 18F-DCFPyl PSMA PET/CT scan).

Three patients will be intravenously administered with a single injection of 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 0, 8 or 18mg of unlabelled TLX592.

TLX592, a humanised, engineered monoclonal antibody HuX592r conjugated with a DOTA chelator and radiolabelled with 64Cu (64Cu-TLX592)

64Cu-DOTA-TLX592

This is a Phase 1 trial of TLX592, a humanised, engineered monoclonal antibody HuX592r conjugated with a DOTA chelator and radiolabelled with 64Cu (64Cu-TLX592). TLX592 is being developed as a PSMA-targeting antibody to be radiolabelled with a therapeutic radiosotope for the treatment of PSMA-expressing tumours, therefore this study has been designed to assess the safety and tolerability, pharmacokinetics, whole body biodistribution and radiation dosimetry of 64Cu-TLX592.

The optimisation dose and imaging conditions will be conducted in prostate cancer patients with with oligometastatic disease ( (defined as 5 sites or less outside of the prostate bed). On determining the optimal dose and imaging conditions, an additional cohort of patients with a higher tumour burden such as multiple metastatic sites across ≥10 regions will be assessed.

Study conduct:

Nine, prostate cancer patients with oligometastatic disease as detected using 68Ga-PSMA-11 or 18F-DCFPyl PSMA PET/CT scanning (defined as 5 sites or less outside of the prostate bed) will be randomised to one of three treatment groups to receive a single injection of:

* Group 1: 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu.
* Group 2: 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 8mg of unlabelled TLX592 (mass dose of 10mg).
* Group 3: 2mg of TLX592, labelled with 300 MBq (± 10%) 64Cu combined with 18mg of unlabelled TLX592 (mass dose of 20mg). If one of the three patients in a specific group experiences a dose-limiting toxicity, three more patients will be treated at the same dose level.

Patients with a higher tumour burden such as multiple metastatic sites across ≥10 regions \[regions: prostate bed, pelvic lumph nodes, skeleton, distant sites (including viscera)\] as detected on 68Ga-PSMA or 18F-DCFPyl PMSA imaging agent will be allocated to a fourth group.

• Group 4: based on the result of Groups 1-3, the optimal dose and imaging timepoints will be selected to treat 3 patients with higher tumour burden (≥10 metastatic sites and/or visceral disease as detected on a 68Ga-PSMA-11 or 18F-DCFPyl PSMA PET/CTscan).

For dosimetry analysis, biodistribution whole body PET/CT imaging will be performed at 1, 4 ± 0.5h, 20 ± 4h, with the option for a an additional two scans to be performed between the 36-120 hours post administration of the investigational product. The additional scans after the 20h timepoint will be at the discretion of the investigator. Patients will be imaged on a Siemens Biographe scanner, offering the possibility of TOF (time-of-flight) and non-TOF reconstruction.

Comparative tumour PET/CT imaging:

On Days 0, 1 and potentially at 36-120h the biodistribution and tumour imaging will be performed using gated or list mode acquisition, for generation of sub-partitioned data.Such data will allow the mathematical generation of statistically independent images for various dose levels, based on the actual dose administered in the trial.

An end of study visit will be conducted on Day 28 ± 2 days. 64Cu-TLX592 images will be centrally analysed for absorbed organ and whole body doses in a standardised fashion. In addition, tumour absorbed doses will be determined for scientific purposes (estimation of achievable tumour doses of therapeutic nuclides labelled to TLX592). All image data analyses will be performed / confirmed centrally.

Pharmacokinetic analysis:

Blood samples will be taken at the following times and counted in a gamma counter:

* Pre-dose
* 1, 4 ± 0.5h, 20 ± 4h and 48 ± 4h after the administration of 64Cu-TLX592.

This study will consist of four groups with the initial three groups undergoing dose escalation and the fourth group will be to confirm the optimal dose and imaging conditions.

64Cu-TLX592 Phase I Safety, PK, Biodistribution and Dosimetry Study (CUPID Study)

A Phase I, Single Centre, Open-label Study of TLX592 to Assess the Safety and Tolerability, Pharmacokinetics, Biodistribution and Radiation Dosimetry in Patients Diagnosed With Prostate Cancer

Treatment emergent adverse events (TEAE) will be classified according to MedDRA (Medical Dictionary for Regulatory Activities), frequency, severity according to NCI CTCAE V5.0, seriousness, and relationship of study treatment will be assessed. Laboratory abnormalities will be assessed according to the NCI CTCAE v.5.0

Patient plasma samples at 0h, 1h, 4 ± 0.5h, 20 ± 4h and 48 ± 4h after the administration of 64Cu-TLX592 will be counted for radioactivity.

On Days 0, Day 1 and potentially at 36-120h after administration of the investigational product, the biodistribution and tumour imaging will be performed. An end of study visit will be conducted on Day 28 ± 2 days. 64Cu-TLX592 images will be centrally analysed for absorbed organ and whole body doses in a standardised fashion. In addition, tumour absorbed doses will be determined for scientific purposes (estimation of achievable tumour doses of therapeutic nuclides labelled to TLX592)

For dosimetry analysis, biodistribution whole body PET/CT imaging will be performed at 1h, 4 ± 0.5h, 20 ± 4h, with the option for a an additional two scans to be performed between the 36-120 hours.

The optimal antibody mass dose and its effect on the biological clearance of 64Cu- TLX592 from blood and radiation dose to tumour will be conducted on Day 0, Day 1 and potentially at 36-120h. The optimal antibody mass dose will be performed using gated or list mode acquisition, for generation of sub-partitioned data. Such data will allow the mathematical generation of statistically independent images for various dose levels, based on the actual dose administered in the trial.

To evaluate the comparability of PET images and PSMA-targeting characteristics between 64Cu-TLX592 and 68Ga-PSMA-11 and 18F-DCFPyl PSMA imaging agents.

Telix Pharmaceuticals (Innovations) Pty Limited

Rare Diseases

Lethal Congenital Contracture Syndrome 2

Pharmaceutical Solutions

Mitogens

In Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.

GSK2849330 solution (100 mg/mL) for infusion diluted in 0.9% sodium chloride to the appropriate concentration for the dose.

GSK2849330

89Zr-GSK2849330 solution for intravenous administration diluted with GSK2849330 Solution for Infusion (unlabelled GSK2849330) with a target radioactivity of 37MBq and a total antibody concentration of 0.4 mg/mL or 1.2 mg/mL.

89Zr-GSK2849330

GSK Clinical Trials

Human epidermal growth factor receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody (mAb) targeting HER3, is a new agent for subjects whose tumors express HER3. This study aims to characterise the biodistribution and dose-receptor occupancy relationship of GSK2849330 in patients with advanced HER3 expressing solid tumours via the use of PET imaging. This study will be conducted in two parts. Part 1 will be the imaging phase where each subject will receive two doses of GSK2849330 containing both Zirconium-89 (89Zr) labelled GSK2849330 and unlabeled GSK2849330. The amount of unlabeled GSK2849330 present in each dose will be varied to explore the effect on target mediated uptake of 89Zr into HER3 expressing tissues and tumors. Subjects will then proceed to the continuation phase (Part 2) for continued treatment with unlabelled GSK2849330. The study is planned to enroll approximately 12-15 subjects.

Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors

An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium to Investigate the Biodistribution of Anti-HER3 Monoclonal Antibody (mAb) GSK2849330 and Characterize Its Dose-receptor Occupancy Relationship in Subjects With Advanced HER3-Positive Solid Tumors

IPD for this study will be made available via the Clinical Study Data Request site.

Regions of interest (RoI) will be outlined from PET-CT images to represent the tissue radioactivity concentration through the values of SUVmean and SUVpeak.

RoIs will be outlined to represent whole organs and include the volumes encircled

Anatomical localization of radiolabel will be evaluated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

Uptake of GSK2849330 in tumors will be estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

Change in uptake parameters following dose 1 and 2 will estimated to establish dose-dependency of inhibition of target mediated uptake of 89Zr-GSK2849330 by unlabeled GSK2849330.

Average radioactivity concentration will be determined and expressed as SUV and is equal to tissue radioactivity concentration normalized by administered amount of radioactivity per body weight.

Features of tumor will include central necrosis, irregular shape, non-uniform uptake and lesion ID

Measurements will include: maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration-time curve (AUC(0-t), AUC(0-Tau) (repeat dosing) and/or AUC(0-Infinity) (single dose), apparent terminal phase elimination rate constant (lambda z) and apparent terminal phase half-life (t½)

AEs and SAEs will be collected from the time the first dose of study treatment is administered until 45 days following discontinuation of study treatment

Clinical laboratory tests will include clinical chemistry, routine urinalysis, haematology laboratory evaluations and additional parameters

LVEF will be assessed as a measure of safety and tolerability measured by echocardiography (ECHO) or multi gated acquisition (MUGA) scans

Vital sign measurements will include systolic and diastolic blood pressure (BP), temperature, and pulse rate

Samples will be analyzed for the presence of anti-GSK2849330 antibodies using a validated immunoelectrochemiluminescent (ECL) assay.

GlaxoSmithKline

Skin and Connective Tissue Diseases

Behaviors and Mental Disorders

Breast Neoplasms

Urinary Bladder Neoplasms

Aggression

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Fibrinolytic Agents

Plasminogen

One injection of 64-Cu-DOTA-AE105 (app. 200 Mbq IV) followed by 3 PET scans 1,3 and 24 hours post injection

One injection of 64Cu-DOTA-AE105 (app. 200 Mbq) followed by Positron Emission Tomography Scan 1, 3 and 24 hours post injection

Injection of 64Cu-DOTA-AE105

Dorthe Skovgaard, MD, Phd

The primary objective of the study is to test a new radiotracer called 64Cu-DOTA-AE105 for PET imaging of uPAR (urokinase plasminogen activator receptor). The tracer has the potential of identifying the invasive cancer phenotype, thereby distinguishing between aggressive and less aggressive tumors. This is a first in human study to test the radiotracer in cancer patients. The biodistribution and tumor uptake will be evaluated by repeated PET imaging (1,3 and 24 hours post injection).

The primary objective of the study is to test a new radiotracer called 64Cu-DOTA-AE105 for PET imaging of uPAR (urokinase plasminogen activator receptor). The tracer has the potential of identifying the invasive cancer phenotype, thereby distinguishing between aggressive and less aggressive tumors. This is a first in human study to test the radiotracer in cancer patients. The biodistribution and tumor uptake will be evaluated by repeated PET imaging (1,3 and 24 hours post injection). The primary end points are Biodistribution and dosimetry of 64Cu-DOTA-AE105. In addition, the quantitative uptake of 64Cu-DOTA-AE105 in tumors and expression of uPAR in tumor tissue obtained by surgery or biopsies (either 14 days before (only biopsies) or after the PET scans) will be compared to validate the image-derived data on UPAR expression

Evaluation of a New Radiotracer (64Cu-DOTA-AE105) for Diagnosing Aggressive Cancer With Positron Emission Tomography

64Cu-DOTA-AE105. Evaluation of a New Radiotracer Targeting uPAR (Urokinase Plasminogen Activator Receptor) for Positron Emission Tomography Imaging of the Invasive Cancer Phenotype. First in Man.

The patients will be PET scanned 1, 3 and 24 hours post injection of the radiotracer 64Cu-DOTA-AE105. These different timepoints will be used for assessment of biodistribution

The patients will be PET scanned 1, 3 and 24 hours post injection of the radiotracer 64Cu-DOTA-AE105. These different timepoints will be used for calculation of dosimetry

Tumor uptake of 64Cu-DOTA-AE105 will be compared with expression of uPAR (using immunohistochemistry and ELISA) in tumor tissue obtained from biopsies/or operative removal of the tumors.

The patients will be PET scanned 1, 3 and 24 hours post injection of the radiotracer 64Cu-DOTA-AE105. These different timepoints will be used for assessment of tumor uptake of 64Cu-DOTA-AE105 will be assessed by PET scans 1, 3 and 24 hours post injection

Rigshospitalet, Denmark

MD, Phd

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Antineoplastic Agents

Radium Ra 223 dichloride

The patients will receive Radium-223 chloride as an escalating dose of either 50, 100 or 200 kBq/kg b.w. (0.0014, 0.0027 or 0.0054 mCi/kg).

The required volume of study drug to be administered to a patient was calculated using the patient's body weight.

Radium-223 chloride (BAY88-8223)

Michael J. Morris, MD

The purpose of the study is to investigate the safety, biodistribution, radiation dosimetry and pharmacokinetics of three intravenous escalating dose levels of Xofigo (Alpharadin).

Within the U.S., the trial is conducted under an IND sponsored by Bayer.

Alpharadin™ (Radium-223 Chloride) Safety and Dosimetry With HRPC That Has Metastasized to the Skeleton

Phase 1, Open-label, Single Ascending-dose Study to Assess Safety, Pharmacokinetics, Biodistribution and Radiation Dosimetry of Intravenous Doses of Alpharadin™ Injection (Radium-223 Chloride) in Patients With HRPC and Skeletal Metastases

Bayer

Radiopharmaceuticals

Single intravenous injection of 10 millicuries of I-131-CLR1404 given on Day 0

I-131-CLR1404

Medical Monitor

The purpose of the study is to investigate the safety, biodistribution, radiation dosimetry and pharmacokinetics of I-131-CLR1404.

I-131-CLR1404 is a small-molecule, phospholipid ether analog that combines lipid-like properties with a cancer therapeutic beta-emitting radioisotope. Cellectar believes that this compound will benefit individuals with cancer due to its selective retention and accumulation in malignant cells versus nonmalignant cells. Preclinical experiments have demonstrated that I-131-CLR1404 significantly slows malignant tumor growth in several mouse tumor models.

Dosimetry Study of I-131-CLR1404 in Patients With Relapsed or Refractory Advanced Solid Tumors

A Phase I, Multi-Center, Open-Label, Dosimetry Study of I-131-CLR1404 in Patients With Relapsed or Refractory Advanced Solid Tumors Who Have Failed Standard Therapy or for Whom No Standard Therapy Exists

Cellectar, Inc

Director Clinical Operations

Respiratory Tract (Lung and Bronchial) Diseases

Gland and Hormone Related Diseases

Digestive System Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Carcinoma, Pancreatic Ductal

Mesothelioma

Mesothelioma, Malignant

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenoma

Neoplasms, Mesothelial

Respiratory Tract Neoplasms

Thoracic Neoplasms

Pleural Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Neoplasms, Female

Endocrine System Diseases

Gonadal Disorders

Carcinoma, Ductal

Adenocarcinoma

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Malignant Mesothelioma

Pancreatic Cancer

Immunoglobulin G

Amatuximab (MORab-009)

Raffit Hassan, M.D.

Background:

- Amatuximab is a cancer treatment drug that targets mesothelin. High levels of this substance are found on some kinds of tumor cells. Lab studies have shown that amatuximab helps the immune system to kill cells that have high levels of mesothelin. However, more research is needed to determine how safe and effective amatuximab is for treating tumors with high levels of mesothelin.

Objectives:

- To assess the safety and effectiveness of amatuximab in treating tumors with high levels of mesothelin.

Eligibility:

- Individuals at least 18 years of age who have a type of cancer that overexpresses mesothelin.

Design:

* Participants will be screened with a medical history and physical exam. They will also have blood tests and tumor assessment studies.
* Participants will have two intravenous doses of amatuximab several hours apart. Researchers will monitor them closely and do frequent blood draws. On the same day and also within 48 hours of the second dose, participants will have imaging studies. These studies will measure how well the amatuximab is working against the cancer.
* Participants will have a third imaging study of the cancer about 1 week after the infusions.
* Participants will have a followup visit 2 weeks after receiving amatuximab. This visit will require blood samples. Four weeks after receiving the drug, researchers will review patients symptoms or side effects. This interview can be done in person or by phone.

Background:

* Amatuximab is a high-affinity monoclonal IgG antibody raised against human mesothelin.
* Mesothelin is a glycosyl-phosphatidyl inositol-linked membrane glycoprotein thought to be involved in tumor metastasis
* Mesothelin is over-expressed in many cancers

Objectives:

-The primary objective is to determine the biodistribution of radiolabeled amatuximab in tumor and nontumor tissues in subjects with mesothelin over-expressing cancers including mesothelioma, pancreatic, ovarian, and non small cell lung cancer.

Eligibility:

* Female or male subjects greater than or equal to 18 years of age;
* Histologically confirmed mesothelin-expressing cancer;
* Transaminases less than or equal to 3 times ULN for mesothelioma, non small cell lung and ovarian cancer;
* Transaminases less than or equal to 5 times ULN for pancreatic cancer with known liver metastasis.

Design:

* This is a single-center, single-dose, open-label, pilot study of MORAb-009 in approximately 20 subjects with mesothelin expressing tumors.
* Indium-radiolabeled MORAb-009 (5mCi) will be administered.
* Serial single photon emission-computerized tomography imaging will be performed to determine binding to tumor and nontumor tissue.
* Subjects will be observed closely for safety and possible development of anti-MORAb-009 antibodies.
* Pharmacokinetics of radiolabeled antibody will be determined with imaging over time.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
64Cu-TLX592 Phase I Safety, PK, Biodistribution and Dosimetry Study (CUPID Study)	NCT04726033	Metastatic Pros...	64Cu-DOTA-TLX59...	-	Telix Pharmaceuticals (Innovations) Pty Limited
Immuno Positron Emission Tomography Study of GSK2849330 in Subjects With Human Epidermal Growth Factor Receptor 3-Positive Solid Tumors	NCT02345174	Cancer Neoplasms	GSK2849330 89Zr-GSK2849330	18 Years -	GlaxoSmithKline
Evaluation of a New Radiotracer (64Cu-DOTA-AE105) for Diagnosing Aggressive Cancer With Positron Emission Tomography	NCT02139371	Breast Cancer Prostate Cancer Urinary Bladder...	Injection of 64...	18 Years - 80 Years	Rigshospitalet, Denmark
Alpharadin™ (Radium-223 Chloride) Safety and Dosimetry With HRPC That Has Metastasized to the Skeleton	NCT00748046	Prostate Cancer Metastases Pharmacokinetic...	Radium-223 chlo...	18 Years -	Bayer
Dosimetry Study of I-131-CLR1404 in Patients With Relapsed or Refractory Advanced Solid Tumors	NCT00925275	Solid Tumors	I-131-CLR1404	18 Years -	Cellectar, Inc
64Cu-TLX592 Phase I Safety, PK, Biodistribution and Dosimetry Study (CUPID Study)	NCT04726033	Metastatic Pros...	64Cu-DOTA-TLX59...	-	Telix Pharmaceuticals (Innovations) Pty Limited
Amatuximab for High Mesothelin Cancers	NCT01413451	Carcinoma, Panc... Mesothelioma Ovarian Neoplas... Carcinoma, Non-...	Amatuximab (MOR...	18 Years - 100 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for biodistribution