PET Imaging of the Immune System Using Analog Probes

October 8, 2021 updated by: Jonsson Comprehensive Cancer Center

PET Imaging of the Immune System Using New Nucleotide Analog Probes

The goal of this proposal is to assess the biodistribution of 18F-Clofarabine, a new tracer developed for use in PET/CT scans. The investigator's hypothesis is this tracer will allow for imaging immune activation in patients with melanoma before and after treatment with immunotherapy.

A maximum of 10 subjects are intended to be included in this study. Each subject will undergo a maximum of two 18F-Clofarabine PET/CT scans, with each visit taking up to 4 hours. The first visit will be prior to the first cycle of immunotherapy treatment, and the second scan will take place 2-4 weeks after the immunotherapy treatment has started.

Prior to the PET scan an IV line will be placed. Blood pressure, heart rate, blood oxygen and ECG will be obtained. Then the 18F-Clofarabine will be injected and the PET/CT scan acquisition started. After a maximum of 120 min of scanning, subjects will undergo again blood pressure, heart rate, blood oxygen and ECG.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a non-interventional pilot study dedicated to PET imaging for patients with metastatic or recurrent advanced cancer melanoma before and after immune therapy interventions with an anti-TIM-3 monoclonal antibody, with or without an anti-PD1 antibody.

PET/CT will be used to investigate the bio-distribution of 18F-Clofarabine in patients with advanced or metastatic melanoma before and 2 to 4 weeks after immune system activating interventions, namely an anti-TIM-3 monoclonal antibody, alone or in combination with an anti-PD1 antibody. Clofarabine is a FDA-approved drug for treatment of relapsed or refractory pediatric acute lymphoblastic leukemia (December 2004) and is gaining importance for treating adult patients with acute myeloid leukemia. Despite extensive preclinical toxicity studies and multiple human phase I studies, the exact bio-distribution of Clofarabine remains unknown. The labeling of Clofarabine with 18F allows the in vivo imaging of its bio-distribution using only minimal concentrations of the therapeutically active doses. The radioactive labeling of clofarabine does not change the parent molecule since a 19F present in the parent compound is simply replaced by an 18F.

The investigators hypothesize that imaging the bio-distribution of clofarabine non-invasively will provide insights into the bio-distribution of the drug in vivo. Imaging the bio-distribution of radiolabeled Clofarabine may help to better understand the side effects caused by therapeutic doses. Importantly, the investigators want to understand if interventions activating the immune system impact the bio-distribution of 18F-Clofarabine. This is because the enzyme dCK that is required to activate the prodrug clofarabine is highly expressed in activated immune cells (3).

Dynamic PET/CT imaging with 18F-Clofarabine will be performed in 10 patients with advanced or metastatic melanoma who have progressed following treatment with an anti-PD-1 antibody. 18F-Clofarabine PET/CT scans will be collected before and 2-4 weeks after treatment with an anti-TIM-3 monoclonal antibody, with or without an anti-PD1 antibody. Imaging can be completed without exposing human subjects to any significant risk. It should be noted, that only trace amounts (nano-molar concentrations in saline solution) of the labeled 18F-Clofarabine will be administered intravenously. Thus, mass effects of the drug and any toxic effects can be ruled out. Tracer concentrations in all organs can be quantified non-invasively in organs which may provide insights into the whole-body drug distribution. Investigators have now seen in humans and non-human primates the exact bio-distribution that one would expect with uptake in bone marrow, spleen, LN and, if patients are young, in thymus. Liver uptake is non-specific and likely due to hepatic clearance via biliary system. There is no retention in other organs which does not mean that there is no low background activity. Tracer uptake is proportional to dCK activity in tissues.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90095
        • University of California, Los Angeles

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

- Patients with advanced or metastatic melanoma who have progressed following treatment with an anti-PD-1 or anti-PD-L1 antibody, who are enrolled in a clinical trial and scheduled to receive an anti-TIM-3 monoclonal antibody, alone or in combination with an anti-PD1 antibody, will be eligible for this study.

Description

Inclusion Criteria:

The following inclusion criteria also apply:

  1. Subject must be able to tolerate PET/CT (i.e. not claustrophobic and able to remain supine)
  2. Subject must be 18 years or older
  3. Participation in a main study of anti-TIM-3

Exclusion Criteria:

  • Patients who meet the exclusion criteria are excluded from this study. 1. Pregnancy

    1. Women of childbearing potential will have to undergo a pregnancy test that will be provided free of charge.
    2. Current knowledge indicates no confirmed detrimental effects to a developing fetus of radiation doses below 10,000 mrem. The radiation dose received from the study procedure is very small in comparison, however, the exclusion criteria is in place to minimize any potential for exposure of a fetus.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
pre cohort
Each subject will undergo a maximum of two 18F-Clofarabine PET/CT scans with each visit taking up to 4 hours. The 18F-Clofarabine PET/CT scans will be performed before the treatment interventions.
Drug: [18F] CFA
pilot study to evaluate the bio-distribution of [18F] CFA, a new tracer for imaging the purine nucleoside biosynthetic pathway, before and after immunotherapy treatment in patients with metastatic or recurrent advanced melanoma.
Other Names:
  • tracer for imaging the purine nucleoside biosynthetic pathway
post cohort
Each subject will undergo a maximum of two 18F-Clofarabine PET/CT scans with each visit taking up to 4 hours. The 18F-Clofarabine PET/CT scans will be performed after the treatment interventions.
Drug: [18F] CFA
pilot study to evaluate the bio-distribution of [18F] CFA, a new tracer for imaging the purine nucleoside biosynthetic pathway, before and after immunotherapy treatment in patients with metastatic or recurrent advanced melanoma.
Other Names:
  • tracer for imaging the purine nucleoside biosynthetic pathway

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
biodistribution of tracer
Time Frame: 6 weeks
The biodistribution of 18F-Clofarabine in melanoma patients
6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jonsson Comprehensive Cancer Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline
Tesaro, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Antoni Ribas, M.D., UCLA/Jonsson Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 10, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 10, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 10, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 18, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 24, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 8, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-001172
  • NCI-2018-01547 (Registry Identifier: CTRP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Malignant Melanoma

Clinical Trials on [18F] CFA

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings