Neoplasms

Symptoms and General Pathology

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Neoplasm Metastasis

Prostatic Neoplasms

Urinary Bladder Neoplasms

Carcinoma, Renal Cell

Kidney Neoplasms

Carcinoma

Lymphatic Metastasis

Urogenital Neoplasms

Urogenital Diseases

Male Urogenital Diseases

Neoplastic Processes

Urologic Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Kidney Diseases

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Renal Cell Carcinoma

Hematinics

Pharmaceutical Solutions

All Drugs and Chemicals

Ferrosoferric Oxide

Parenteral Nutrition Solutions

Ferumoxytol

3 MRIs: pre-infusion, 24 and 48 hours post-infusion

Magnetic Resonance Imaging (MRI)

Ismail B Turkbey, M.D.

Background:

People with prostate, bladder, or kidney cancer often have their cancer spread (metastasize) to lymph nodes. It is important for your doctor to know if this has occurred but currently it can be hard to determine if this has occurred on standard imaging studies like computed tomography (CT) or magnetic resonance imaging (MRI). This study uses an agent called Ferumoxytol to identify lymph nodes that might be involved by cancer.

Objective:

- To see how well Ferumoxytol can detect lymph node metastases in patients with prostate, bladder, or kidney cancer.

Eligibility:

-Adults over age 18 with prostate, bladder, or kidney cancer with lymph node involvement.

Design:

* Participants will be screened with a medical history.
* Participants will have blood drawn and a physical exam. Their vital signs will be measured. They will answer questions about their health and current medications.
* Participants should not have a history of iron overload or have an allergy to Ferumoxytol.
* Participants will have a magnetic resonance imaging (MRI) scan. The scanner is a metal cylinder with a strong magnetic field. Participants will lie on a table that slides in and out of the scanner. They will have a standard sensor, known as a coil, wrapped around their abdomen to improve the scan. This is like a small blanket with wiring inside. Participants will need to lie still on the scanning table for about 1 hour.
* Participants will have an ultrasound. This uses harmless sound waves to provide pictures of organs or tissues inside the body.
* Participants will receive an injection of Ferumoxytol through an intravenous line. A very thin plastic tube will be inserted into a vein in order to inject the agent.
* Participants will have another MRI and ultrasound 24 and 48 hours after injection.
* The study will follow participants medical course for at least 1 year.

Background:

* Conventional imaging modalities (e.g. computed tomography \[CT\] and magnetic resonance imaging \[MRI\]) are currently used for the detection of lymph node metastases in many cancer types, including prostate, bladder and kidney cancers, however diagnosis is based on node enlargement which is neither sensitive nor specific (i.e. small nodes harbor metastases, large nodes can be hyperplastic).
* As a consequence, the standard of care is to remove numerous lymph nodes during surgery or to biopsy enlarged nodes to ascertain lymph node status.
* In 2003 Dextran coated ultra small superparamagnetic iron oxide particles (USPIO), also known as Ferumoxtran-10 (Combidex, AMAG Pharmaceuticals, Inc. Lexington, Massachusetts (MA), United States (US)) was shown to localize lymph node metastases with much greater accuracy than unenhanced MRI. Although a large study in prostate cancer was successful, and Food and Drug Administration (FDA) Advisory Panel did not recommend approval and the company abandoned the agent.
* In 2009 Ferumoxytol (Feraheme AMAG Pharmaceuticals, Inc. Lexington, MA, United States (US)) a semi-synthetic carbohydrate coated, magnetic iron oxide preparation similar to ferumoxtran 10 was approved for iron replacement therapy. Like ferumoxtran 10, this compound is taken up by normal lymph nodes and excluded from malignant nodal tissue.
* Results of a recent National Cancer Institute (NCI) trial (11-C-0098) in 15 patients revealed that using the dose of 7.5 mg/kg Fe is safe and yields homogenous and accurate signal changes in benign lymph nodes in comparison with the 4 and 6 mg/kg Fe doses. This dose was further tested in 5 patient's with known or suspected nodal involvement from prostate cancer and in four of five patients positive lymph nodes had a lower signal drop than the benign nodes. The one case in which there was uptake by positive nodes may have been on a vascular basis. This pilot study stimulated interest in a larger study involving a variety of cancer types.

Primary Objective:

-To compare the difference in signal between metastatic and normal nodes in prostate, kidney and bladder cancer patients.

Eligibility

* Subject must be greater than or equal to 18 years old.
* Eastern Cooperative Oncology Group Performance score of 0 to 2.
* There are 3 parallel arms in this study. All patients must have evidence of lymph node involvement (with a short axis diameter greater than or equal to 1.5 cm).
* In addition:
* Arm 1: Subject must have a documented diagnosis of prostate cancer.
* Arm 2: Subject must have a documented diagnosis of bladder cancer (transitional cell carcinoma).
* Arm 3: Subject must have a documented diagnosis of kidney cancer (all renal cell cancer types).

Design:

* This is a single site 3-arm (arm 1=prostate cancer, arm 2=bladder cancer, arm 3=kidney cancer) study enrolling 50 evaluable patients (30 evaluable in each arm 1, 10 evaluable in arms 2 and 3) with documented prostate, bladder or kidney cancer with evidence of lymph node involvement \[with a size of greater than or equal to 1.5 cm measured on conventional imaging (e.g. CT, MRI)\].
* All subjects will undergo pre-infusion, 24, 48 hours post-Ferumoxytol infusion (dose of 7.5mg/kg Fe) MRI consisting of T1 weighted (W), T2W and T2\*W 3 Tesla MRI.
* Imaging will be correlated with histology of resected or biopsied lymph nodes when available. Occasionally, patients may not undergo biopsy or surgical excision of their lymph nodes. This may occur if their lymph nodes are overtly large and therefore highly likely to represent lymph node involvement. In such cases, patients will be evaluated with clinical follow up which typically occurs every three months in most NCI protocols. If the lesion demonstrates growth or regression based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on these follow up studies' then the lesion will be considered positive for tumor. If it is stable for at least one year, then it will be considered non-malignant. The MR imaging analysis will be intra-patient.
* Patients will also undergo ultrasound examination of imageable lymph nodes (e.g. inguinal nodes) at pre-infusion and 24, 48 hours post-Ferumoxytol infusion time points. The signal changes at post-infusion ultrasound will be visually evaluated to determine if the uptake of ferumoxytol alters sonographic features.

Study of Ferumoxytol Enhanced MRI for Detecting Lymph Node Metastases in Prostate, Bladder, and Kidney Cancers

Evaluation of Ferumoxytol Enhanced MRI for the Detection of Lymph Node Metastases in Genitourinary (Prostate, Bladder and Kidney) Cancers

Visible nodes were quantified with manually contoured regions of interest on axial T2\*W MRI to obtain the mean signal intensity (SInode). The SI of the visible lymph node was normalized using the mean SI of the adjacent muscle tissue on the same slice (SImuscle). The following equation was used to obtain the normalized SI from the lymph node (SInormal): SInormal=SInode/SImuscle. The calculation formula was 100% \* ((SInormal(24hrs)- SInormal(baseline))/ SInormal(baseline)).This image processing method was performed at baseline, 24-hours post-injection MRI studies to define the SI change differences between benign and malignant lymph nodes from baseline to 24 hours post injection.

Visible nodes were quantified with manually contoured regions of interest on axial T2\*W MRI to obtain the mean signal intensity (SInode). The SI of the visible lymph node was normalized using the mean SI of the adjacent muscle tissue on the same slice (SImuscle). The following equation was used to obtain the normalized SI from the lymph node (SInormal): SInormal=SInode/SImuscle. The calculation formula was 100% \* ((SInormal(48hrs)- SInormal(baseline))/ SInormal(baseline))). This image processing method was performed at baseline, 48-hours post-injection MRI studies to define the SI change differences between benign and malignant lymph nodes from baseline to 48 hours post-injection.

Patients will undergo ultrasound examination of imageable lymph nodes at pre-infusion, 24 hours and 48 hours. The signal changes at post-infusion ultrasound will be visually evaluated to determine if the uptake of ferumoxytol alters sonographic features.

Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

National Cancer Institute (NCI)

Principal Investigator

Results are available for 39/45 subjects because 6 were deemed screen failures following enrollment.

Ferumoxytol + Magnetic Resonance Imaging (MRI)

Ferumoxytol: 7.5mg/kg intravenous (IV) infusion

Magnetic Resonance Imaging (MRI): 3 MRIs: pre-infusion, 24 and 48 hours post-infusion

Prostate Cancer

Bladder Cancer

Kidney Cancer

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Ismail B. Turkbey

% change from baseline to 24h in metastatic nodes

% change from baseline to 24h in benign nodes

Due to low accrual in the bladder and renal arms, all three diseases (Prostate Cancer, Bladder Cancer and Kidney Cancer) were combined together for analysis.

Ferumoxytol + Magnetic Resonance Imaging (MRI)

Ferumoxytol: 7.5mg/kg intravenous (IV) infusion

Magnetic Resonance Imaging (MRI): 3 MRIs: pre-infusion, 24 and 48 hours post-infusion

All Participants

Results are available for 39/43 subjects because 4 were screen failures.

Percentage Change (From Baseline to 24 Hours) Between Metastatic and Benign Nodes

% change from baseline to 48h in metastatic nodes

% change from baseline to 48h in benign nodes

Due to low accrual in the bladder and renal arms, all three diseases (Prostate Cancer, Bladder Cancer and Kidney Cancer) were combined together for analysis.

Ferumoxytol + Magnetic Resonance Imaging (MRI) Ferumoxytol: 7.5mg/kg intravenous (IV) infusion Magnetic Resonance Imaging (MRI): 3 MRIs: pre-infusion, 24 and 48 hours post-infusion

Percentage Change for Imaging (From Baseline to 48 Hours) Between Metastatic and Benign Nodes

The analysis for this outcome measure was not done because most of the patients had deeply located lymph nodes and logistically ultrasonography analysis was not possible.

Percent Change in Signal Difference Within Metastatic Nodes in Prostate, Kidney, Bladder Cancer Patients at Ultrasonography

Number of Participants With Serious and Non-Serious Adverse Events

Overall Study

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

Nutritional and Metabolic Diseases

Recurrence

Multiple Myeloma

Neoplasms, Plasma Cell

Amyloidosis

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Proteostasis Deficiencies

Metabolic Diseases

Antineoplastic Agents

Micronutrients

Mineral

Antibodies

Antibodies, Monoclonal

Daratumumab

Immunoglobulins

Copper

Copper Supplement

Patients receive daratumumab IV over 10-45 minutes, and within 6 hours, patients receive copper 64Cu-DOTA-daratumumab IV on day 0. Patients undergo PET on days 1 and 2.

Imaging Agent

Positron Emission Tomography

Pharmacological Study

Amrita Krishnan, MD

This pilot phase I clinical trial studies how well copper 64Cu-DOTA-daratumumab positron emission tomography works in diagnosing patients with multiple myeloma that has come back. Diagnostic procedures, such as copper 64Cu-DOTA-daratumumab positron emission tomography, may help evaluate the extent of multiple myeloma in patients prior to the initiation of treatment and ultimately monitor disease status/response during and post treatment.

PRIMARY OBJECTIVES:

I. To assess safety and tolerability of unlabeled daratumumab followed by 64Cu-DOTA-daratumumab positron emission tomography, at each dose level, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

I. Generate initial estimates of the biodistribution of the 64Cu-DOTA-daratumumab and the preferred dose of cold antibody.

II. Determine the dose of pre-administered unlabeled daratumumab that optimizes image quality of 64Cu-anti-CD38 (daratumumab)-NHS-DOTA.

III. Evaluate the sensitivity of 64Cu-anti-CD38 (daratumumab)-NHS-DOTA in detecting lesions compared to 18F fludeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scanning.

OUTLINE:

Patients receive daratumumab intravenously (IV) over 10-45 minutes, and within 6 hours, patients receive copper 64Cu-DOTA-daratumumab IV on day 0. Patients undergo PET on days 1 and 2.

After completion of study, patients are followed up for 7 days and then at 2 weeks.

Copper 64Cu-DOTA-Daratumumab Positron Emission Tomography in Diagnosing Patients With Relapsed Multiple Myeloma

A Pilot/Feasibility Trial of 64Cu-DOTA-Daratumumab Positron Emission Tomography in Patients With Newly Diagnosed or Relapsed Multiple Myeloma

Will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03. Observed toxicities will be summarized, for all dose levels, in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study agent(s) and reversibility or outcome.

Will be determined by copper 64Cu-DOTA-daratumumab positron emission tomography

City of Hope Medical Center

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Squamous Cell

Panitumumab

Antineoplastic Agents, Immunological

Patients receive loading dose of panitumumab IV over 15 minutes followed by 111In-panitumumab IV bolus on day 0. Patients then undergo SPECT/CT scan between day 1 and day of standard of care surgery (up to day 5). During standard of care surgery, patients receive local injection of optical dye per surgeon's preference and undergo intraoperative and NIR imaging. Patients additionally undergo blood sample collection during screening and ECG during screening, on day 0, and on day 15 if indicated.

Indium In 111 Panitumumab

Single Photon Emission Computed Tomography

Computed Tomography

Surgical Procedure

Imaging agent

Intraoperative Imaging

Near Infrared Imaging

Electrocardiography

Biospecimen Collection

Vanderbilt-Ingram Services for Timely Access

Vanderbilt-Ingram Service Services for Timely Access

Eben Rosenthal, MD

This phase I trial tests the safety and effectiveness of indium In 111 panitumumab (111In-panitumumab) for identifying the first lymph nodes to which cancer has spread from the primary tumor (sentinel lymph nodes) in patients with head and neck squamous cell carcinoma (HNSCC) undergoing surgery. The most important factor for survival for many cancer types is the presence of cancer that has spread to the lymph nodes (metastasis). Lymph node metastases in patients with head and neck cancer reduce the 5-year survival by half. Sometimes, the disease is too small to be found on clinical and imaging exams before surgery. 111In-panitumumab is in a class of medications called radioimmunoconjugates. It is composed of a radioactive substance (indium In 111) linked to a monoclonal antibody (panitumumab). Panitumumab binds to EGFR receptors, a receptor that is over-expressed on the surface of many tumor cells and plays a role in tumor cell growth. Once 111In-panitumumab binds to tumor cells, it is able to be seen using an imaging technique called single photon emission computed tomography/computed tomography (SPECT/CT). SPECT/CT can be used to make detailed pictures of the inside of the body and to visualize areas where the radioactive drug has been taken up by the cells. Using 111In-panitumumab with SPECT/CT imaging may improve identification of sentinel lymph nodes in patients with head and neck squamous cell cancer undergoing surgery.

PRIMARY OBJECTIVE:

I. Assess the safety of indium In 111 panitumumab (111In-panitumumab) as a molecular imaging agent in patients with HNSCC.

SECONDARY OBJECTIVE:

I. Compare sensitivity and specificity of identifying sentinel lymph nodes by systemic injection of 111In-panitumumab prior to day of surgery versus conventional local injection with an optical dye at the time of surgery.

EXPLORATORY OBJECTIVES:

I. Determine if systemic injection of 111In-panitumumab can identify tumor-positive lymph nodes on preoperative SPECT/CT.

II. When preoperative imaging information (eg, fludeoxyglucose F 18 \[18F-FDG\] positron emission tomography \[PET\]/CT and/or magnetic resonance imaging \[MRI\]) data is available:

IIa. Evaluate the sensitivity, specificity, and negative predictive value of 111In-panitumumab SPECT/CT findings to the sensitivity, specificity, and negative predictive value of preoperative MRI in identifying metastatic lymph nodes (histopathological results will serve as the gold standard).

IIb. Evaluate the sensitivity, specificity, and negative predictive value of 111In-panitumumab SPECT/CT findings to the sensitivity, specificity, and negative predictive value of preoperative 18F-FDG PET/CT in identifying metastatic lymph nodes (histopathological results will serve as the gold standard).

OUTLINE:

Patients receive loading dose of panitumumab intravenously (IV) over 15 minutes followed by 111In-panitumumab IV bolus on day 0. Patients then undergo SPECT/CT scan between day 1 and day of standard of care surgery (up to day 5). During standard of care surgery, patients receive local injection of optical dye per surgeon's preference and undergo intraoperative and near infrared (NIR) imaging. Patients additionally undergo blood sample collection during screening and electrocardiography (ECG) during screening, on day 0, and on day 15 if indicated.

Patients are followed for up to 15 days after last dose of study medication.

Evaluating 111In Panitumumab for Nodal Staging in Head and Neck Cancer

Toxicity graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Summarized by grade, severity and type

Will compare the sensitivity of systemic injection of 111In-panitumumab for identifying sentinel lymph nodes to the sensitivity of conventional local injection with an optical dye at the time of surgery. Means and standard deviations for continuous characteristics will be presented. Frequency statistics will be presented for categorical variables. Graphical tools may be used to assess distributional properties of continuous variables.

Will compare the specificity of systemic injection of 111In-panitumumab for identifying sentinel lymph nodes to the sensitivity of conventional local injection with an optical dye at the time of surgery. Means and standard deviations for continuous characteristics will be presented. Frequency statistics will be presented for categorical variables. Graphical tools may be used to assess distributional properties of continuous variables.

American Cancer Society, Inc.

Vanderbilt-Ingram Cancer Center

Professor of Medicine

HS-196 will be administered intravenously as a single dose

HS-196

H. Kim Lyerly, MD

HS-196 is near infrared red (NIR)-tethered HSP90 inhibitor for clinical imaging of selective tumor binding. HS-196 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a contrast agent (near infrared (NIR) dye) that can be used for imaging. HS-196 can freely enter tumor cells to selectively bind Hsp90. Due to the the NIR dye, HS-196 accumulation in the malignant cells allows for specific visualization of tumors within the body.

The product to be tested under this IND, HS-196, is a tumor imaging agent.

Hsp90 (heat shock protein 90) is a chaperone protein that aids in the folding, stabilization, and degradation of cellular proteins and is found in virtually all living organisms. Cancer cells in particular have high expression of Hsp90. Hsp90 has three structural domains including an N-terminal domain that contains an ATP binding site. Small molecule inhibitors of HSP90 (Hsp90i) can selectively and competitively to the Hsp90 ATP binding domain. HS-196 consists of a HSP90 inhibitor that binds competitively to the Hsp90 ATP binding domain connected by a linker to a contrast agent (near infrared (NIR) dye) that can be used for imaging. HS-196 can freely enter tumor cells to selectively bind Hsp90. Due to the the NIR dye, HS-196 accumulation in the malignant cells allows for specific visualization of tumors within the body.

HS-196 will be used in this investigation for the imaging of solid tumors The objectives of the study are to determine the dose of HS-196 that achieves the greatest ratio of tumor to normal tissue fluorescence in patients with malignancy, the safety of HS-196 administration in patients with malignancy, the average radiant efficiency in resected tumors following HS-196 administration, the localization of the HS-196 by microscopy of tumor slices, and the PK metrics of HS-196 when administered to patients.

A Study of HS-196, an HSP90 Inhibitor-linked NIR Probe for Solid Malignancies

A Phase I Study of HS-196, an HSP90 Inhibitor-linked Near Infrared Probe for Detection of Solid Malignancies

Ratio of tumor to normal tissue fluorescence

Safety of HS-196 administration in patients with malignancy

The average radiant efficiency in resected tumors following HS-196 administration.

Localization of the HS-196 by microscopy of tumor slices.

PK metrics of HS-196 when administered IV to patients

Herbert Lyerly

Professor

Mouth and Tooth Diseases

Mouth Neoplasms

Lip Neoplasms

Mouth Diseases

Stomatognathic Diseases

Oral Squamous Cell Carcinoma

Oral Cancer

Lip and Oral Cavity Cancer

Patients receive an imaging agent via injection and undergo planar imaging and SPECT/CT over 1-2 hours. Patients then undergo SLN biopsy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Ferumoxytol Enhanced MRI for Detecting Lymph Node Metastases in Prostate, Bladder, and Kidney Cancers	NCT02141490	Prostate Cancer Bladder Cancer Kidney Cancer	Ferumoxytol Magnetic Resona...	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
Copper 64Cu-DOTA-Daratumumab Positron Emission Tomography in Diagnosing Patients With Relapsed Multiple Myeloma	NCT03311828	Recurrent Plasm... Plasma Cell Mye... Secondary Amylo...	Daratumumab Imaging Agent Positron Emissi... Pharmacological...	18 Years -	City of Hope Medical Center
Copper 64Cu-DOTA-Daratumumab Positron Emission Tomography in Diagnosing Patients With Relapsed Multiple Myeloma	NCT03311828	Recurrent Plasm... Plasma Cell Mye... Secondary Amylo...	Daratumumab Imaging Agent Positron Emissi... Pharmacological...	18 Years -	City of Hope Medical Center
Evaluating 111In Panitumumab for Nodal Staging in Head and Neck Cancer	NCT05901545	Head and Neck S... Recurrent Head ...	Panitumumab Indium In 111 P... Single Photon E... Computed Tomogr... Surgical Proced... Imaging agent Intraoperative ... Near Infrared I... Electrocardiogr... Biospecimen Col...	19 Years -	Vanderbilt-Ingram Cancer Center
Study of Ferumoxytol Enhanced MRI for Detecting Lymph Node Metastases in Prostate, Bladder, and Kidney Cancers	NCT02141490	Prostate Cancer Bladder Cancer Kidney Cancer	Ferumoxytol Magnetic Resona...	18 Years - 99 Years	National Institutes of Health Clinical Center (CC)
A Study of HS-196, an HSP90 Inhibitor-linked NIR Probe for Solid Malignancies	NCT03333031	Solid Tumor	HS-196	18 Years - 99 Years	Duke University
Comparing Sentinel Lymph Node (SLN) Biopsy With Standard Neck Dissection for Patients With Early-Stage Oral Cavity Cancer	NCT04333537	Buccal Mucosa S... Floor of Mouth ... Gingival Squamo... Hard Palate Squ... Lip Squamous Ce... Lower Alveolar ... Oral Cavity Squ... Retromolar Trig... Stage I Lip and... Stage II Lip an... Tongue Squamous... Upper Alveolar ...	Computed Tomogr... Imaging Agent Neck Dissection Planar Imaging Sentinel Lymph ... Single Photon E...	18 Years -	NRG Oncology

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