Malignant MelanomaNCT03409419
PET Imaging of the Immune System Using Analog Probes
An observational study of Malignant Melanoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Melanoma
- What is being tested?
- [18F] CFA
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2018to 10 Nov 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- The following inclusion criteria also apply:
- Subject must be able to tolerate PET/CT (i.e. not claustrophobic and able to remain supine)
- Subject must be 18 years or older
- Participation in a main study of anti-TIM-3
Who cannot join
- Patients who meet the exclusion criteria are excluded from this study. 1. Pregnancy
- Women of childbearing potential will have to undergo a pregnancy test that will be provided free of charge.
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles
Los Angeles, California, 90095
About this study
Official title: 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.
Read the 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.
- Conditions
- Malignant Melanoma
- Being tested
- [18F] CFA
- Keywords
- Advanced, Recurrent, Immune Therapy
- Medical subject headings
- Melanoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[18F] CFADrug
Also called tracer for imaging the purine nucleoside biosynthetic pathway
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: [18F] CFA | |
| 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. Receives: Drug: [18F] CFA |
What is being measured
The primary outcome is the main question the study is designed to answer.
biodistribution of tracer
The biodistribution of 18F-Clofarabine in melanoma patients
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2018
- Study start10 Apr 2018
- Primary completion10 Nov 2020
- Study completion10 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant MelanomaStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Tesaro, Inc., GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Antoni Ribas, M.D., Principal investigator, UCLA/Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03409419
- Sponsor's protocol ID
- 17-001172
- Other IDs
- NCI-2018-01547
- Status last verified
- Oct 2021
- First submitted
- 18 Jan 2018
- Last updated
- 12 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PET Imaging of the Immune System Using New Nucleotide Analog Probes
- ClinicalTrials.gov ID
- NCT03409419
- Acronym / sponsor ID
- 17-001172
- Conditions
- Malignant Melanoma
- Keywords
- Advanced, Recurrent, Immune Therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Tesaro, Inc., GlaxoSmithKline
- Study start
- 10 Apr 2018 (actual)
- Primary completion
- 10 Nov 2020 (actual)
- Study completion
- 10 Nov 2020 (actual)
- First posted
- 24 Jan 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| pre cohort | – | Drug: [18F] CFAEach 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. |
| post cohort | – | Drug: [18F] CFAEach 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- Subject must be able to tolerate PET/CT (i.e. not claustrophobic and able to remain supine)
- Subject must be 18 years or older
- Participation in a main study of anti-TIM-3
Key exclusion criteria (3 listed)
- Patients who meet the exclusion criteria are excluded from this study. 1. Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| [18F] CFAAlso: tracer for imaging the purine nucleoside biosynthetic pathwaypilot 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. | Drug | post cohort, pre cohort |
Primary outcome
biodistribution of tracer
Time frame: 6 weeks
The biodistribution of 18F-Clofarabine in melanoma patients
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Antoni Ribas, M.D. principal investigator
UCLA/Jonsson Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malignant Melanoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
biodistribution of tracer (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2021.