Using a PET Imaging Agent, 18F-Clofarabine (CFA), to Measure Deoxycytidine Kinase Activity in Metastatic Cancer

Sponsor

Omar Mian (Other)

Overall Status

Recruiting

CT.gov ID

NCT05065736

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether a new type of imaging study, called 18F-Clofarabine (CFA) PET/CT, can be used to image cancer pyrimidine metabolism in participants.

PET (positron emission tomography) imaging is a way of looking at cancers that can reveal cancer metabolism. Presently, however, there are no imaging agents in routine use to look at an aspect of cancer metabolism (pyrimidine metabolism) that dictates whether certain cancer drugs, e.g., gemcitabine, are likely to be taken into the cancer cells. This clinical trial will be testing whether 18F-Clofarabine (CFA) could be an imaging agent to measure this aspect of cancer metabolism.

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cancer Carcinoma Adenocarcinoma	Drug: 18F-Clofarabine	Early Phase 1

Detailed Description

The participants will receive a CFA injection into a vein in their arm. The imaging drug is attracted to and taken into certain cells in the body, including cancer cells. 18F-Clofarabine (CFA) is experimental because it is not approved by the Food and Drug Administration (FDA).

The participants will be observed for side effects, and about 1 hour later, they will receive a PET/CT scan. Additionally, they will be contacted the next day to inquire again about any side effects. If the participant's routine care involves repeat imaging of cancer, then the CFA PET/CT scan will be repeated at that time, which could be a month to about 4 months after the first CFA PET/CT scan.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Diagnostic

Official Title:

18F-Clofarabine (CFA) as a PET Imaging Agent to Measure Deoxycytidine Kinase (DCK) Activity in Metastatic Cancer, as a Candidate Predictive Biomarker for Response to DCK-dependent Drugs Such as Gemcitabine

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 18F-Clofarabine 18F-Clofarabine as PET imaging agent for measuring the activity of deoxycytidine kinase (DCK) in various normal and abnormal tissues in cancer participants before and after therapy	Drug: 18F-Clofarabine The participants enrolled will receive a baseline CFA PET/CT evaluation. Then, the participants will undergo the routine follow up would normally occur for their cancer and its treatment. If this routine follow up and care involves repeat imaging of the cancer, then the CFA PET/CT scan will be repeated at that time (timed according to standard-of-care follow-up imaging), which is expected between a month to about 4 months after the first CFA PET/CT scan. The study period will end 24 hours after this repeat PET/CT scan.

Arm

Intervention/Treatment

Experimental: 18F-Clofarabine

18F-Clofarabine as PET imaging agent for measuring the activity of deoxycytidine kinase (DCK) in various normal and abnormal tissues in cancer participants before and after therapy

Drug: 18F-Clofarabine

The participants enrolled will receive a baseline CFA PET/CT evaluation. Then, the participants will undergo the routine follow up would normally occur for their cancer and its treatment. If this routine follow up and care involves repeat imaging of the cancer, then the CFA PET/CT scan will be repeated at that time (timed according to standard-of-care follow-up imaging), which is expected between a month to about 4 months after the first CFA PET/CT scan. The study period will end 24 hours after this repeat PET/CT scan.

Outcome Measures

Primary Outcome Measures

Evaluate CFA as a PET imaging agent [up to 60 minutes after CFA PET]
Establish the image-based biodistribution of CFA, a new tracer for imaging DCK enzyme activity. DCK converts the inactive prodrug clofarabine into its active form. Thus, the degree of DCK expression in normal and abnormal tissues may predict drug effects and effectiveness. The uptake of the radiotracer (SUVs) will be measured quantitatively from PET images taken at 60 min post-injection of [18F]CFA.

Secondary Outcome Measures

Correlate CFA uptake with conventional imaging [up to 3 months after CFA PET]
Correlate CFA uptake with conventional anatomic imaging using RECIST criteria to establish change over time and differences from participants' baseline scans.
Correlate CFA uptake with PFS [up to 12 months after CFA PET]
Correlate changes in CFA uptake (SUV) with disease progression as determined by standard of care surveillance imaging.
Correlate CFA uptake with OS [up to 12 months after CFA PET]
Correlate changes in CFA uptake with participant outcomes as measured by all cause mortality/overall survival (OS).
Adverse Events [within 48 hrs of radiotracer administration]
Proportion of participants who develop any side effects/adverse events associated with radiotracer infusions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically proven carcinoma or adenocarcinoma. Histologies other than carcinoma/adenocarcinoma will not be eligible.
Subjects must have metastatic disease, confirmed by imaging, typically a CT scan of the chest/abdomen/pelvis.
Subjects must have measurable disease per RECIST 1.1
Over 18 years of age
ECOG performance status 0-1
Adequate organ function as defined by the following criteria:

Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) and serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) <= 2.5 x laboratory upper limit of normal (ULN)

Total serum bilirubin <= 2.0 x ULN

Absolute neutrophil count (ANC) >= 1500/uL

Platelets >= 75,000/uL

Hemoglobin >= 8.0 g/dL

Serum calcium <= 12.0 mg/dL

Serum creatinine <= 2.9 mg/dL

Subjects must have the ability to understand and the willingness to sign a written informed consent document
Patient is able to remain still for the duration of the imaging procedure (up to one hour).

Exclusion Criteria:

Within 6 months prior to enrollment on this study: myocardial infarction, severe/unstable angina, severe peripheral vascular disease (claudication) or procedure on peripheral vasculature, coronary/peripheral artery bypass graft, New York Heart Association grade II or greater congestive heart failure, cerebrovascular accident or transient ischemic attack, clinically significant bleeding or pulmonary embolism.
Pregnancy or breastfeeding (pregnant or breastfeeding women are excluded from this study because study drugs have the potential for teratogenic or abortifacient effects.
Other severe acute or chronic medical or psychiatric conditions or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study.