18F-Clofarabine PET Imaging for Cancer

Overseen By Roberto Vargas, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Roberto Vargas

Disqualifiers: Heart disease, Stroke, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

4 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new imaging method, 18F-Clofarabine PET/CT, can visualize how cancer cells process certain substances. Researchers hope to understand if specific cancer drugs will be absorbed by the cancer cells. The trial seeks individuals with proven metastatic cancer, meaning their cancer has spread to other parts of the body. Participants should also be able to remain still for about an hour during the imaging process.

As an Early Phase 1 trial, this research focuses on understanding how the imaging method works in people, offering participants a chance to contribute to pioneering cancer research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What prior data suggests that 18F-Clofarabine PET/CT imaging is safe for cancer patients?

Research has shown that 18F-Clofarabine is being studied as a new tool to observe how cancer uses energy. Studies have examined the safety of 18F-Clofarabine in patients, helping to understand how the body processes it and any potential side effects.

For example, one study examined how 18F-Clofarabine moves through the body and its effects. The results indicated that it was generally well-tolerated, with most participants experiencing no serious side effects. No major negative side effects were found, suggesting that 18F-Clofarabine appears safe for use in imaging. However, as this is an early study, further research is needed to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about 18F-Clofarabine because it offers a new way to visualize cancer activity through PET imaging, specifically by measuring the activity of an enzyme called deoxycytidine kinase (DCK) in tissues. Unlike standard imaging techniques, which often provide static images of tumors, 18F-Clofarabine can help reveal how active the cancer is before and after treatment. This could lead to more personalized treatment plans and a better understanding of how well a treatment is working in real time.

What evidence suggests that 18F-Clofarabine PET/CT is effective for imaging cancer metabolism?

Research has shown that 18F-Clofarabine, which participants in this trial will receive, could be a useful tool for PET scans in cancer patients. It helps doctors observe how cancer cells use certain substances, potentially affecting treatment efficacy. This imaging might identify if cancer cells are likely to absorb drugs like gemcitabine. Early studies suggested that 18F-Clofarabine can safely measure the activity of an enzyme called deoxycytidine kinase (DCK) in cancer tissues. This could enhance doctors' ability to understand and predict patient responses to treatment. ^{3 4 5 6 7}

Who Is on the Research Team?

Roberto Vargas, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic carcinoma or adenocarcinoma, confirmed by imaging. Participants must have measurable disease, be able to stay still for an hour during imaging, and have normal organ function levels. It's not suitable for those with recent severe heart issues, significant bleeding, stroke risks, or pregnant/breastfeeding women.

Inclusion Criteria

I am over 18 years old.

I can stay still for up to an hour for a scan.

My cancer is confirmed as carcinoma or adenocarcinoma.

Exclusion Criteria

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

I have not had any major heart problems in the last 6 months.

Pregnancy or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Observation

Participants receive a CFA injection and undergo a PET/CT scan to measure DCK activity. They are observed for side effects.

1 day

1 visit (in-person)

Follow-up

Participants are contacted the next day to inquire about any side effects. If routine care involves repeat imaging, the CFA PET/CT scan may be repeated up to 365 days later.

up to 12 months

1 follow-up contact (virtual), potential additional imaging visits

What Are the Treatments Tested in This Trial?

Interventions

• 18F-Clofarabine

Trial Overview The study tests if a new PET/CT imaging agent called 18F-Clofarabine (CFA) can effectively image cancer metabolism related to pyrimidine metabolism—a factor in how well certain cancer drugs work.

How Is the Trial Designed?

Group I: 18F-Clofarabine Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Roberto Vargas

Lead Sponsor

Trials

1

Recruited

4+

Omar Mian

Lead Sponsor

Trials

2

Recruited

20+

Published Research Related to This Trial

Clofarabine, a purine nucleoside analog, has shown efficacy in treating pediatric patients with relapsed or refractory acute lymphoblastic leukemia, achieving complete remission rates of 12% and partial remission rates of 10% in a study of 61 patients.

The treatment is associated with significant adverse events, primarily hematologic issues like anemia and leukopenia, as well as gastrointestinal symptoms and infections, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clofarabine: in pediatric patients with acute lymphoblastic leukemia. Curran, MP., Perry, CM.[2018]

In a phase I clinical trial involving 15 patients with recurrent/refractory leukemia, clofarabine was well tolerated at a dose of 50 mg/m/d for 5 days, showing minimal treatment-related mortality in this high-risk group.

The treatment led to quick hematopoietic recovery, with median times to neutrophil and platelet engraftment of 11 and 16 days, respectively, although 73.3% of patients ultimately died, primarily due to disease relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Donor Transplantation Using a Novel Clofarabine-containing Conditioning Regimen for Very High-risk Hematologic Malignant Neoplasms. Sharma, A., Kang, G., Sunkara, A., et al.[2019]

Clofarabine is an effective treatment for hematologic malignancies, including acute lymphoblastic leukemia and acute myeloid leukemia, and is already approved for use in pediatric patients after two prior therapies.

Clinical trials indicate that clofarabine works well both alone and in combination with other drugs for adult myeloid leukemia, showing promise particularly in older patients and those with challenging genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clofarabine: a new treatment option for patients with acute myeloid leukemia. Larson, ML., Venugopal, P.[2018]

Clofarabine, a treatment for acute leukemia, shows a median cerebrospinal fluid (CSF) penetration of only 5%, indicating limited ability to reach the central nervous system, but the levels achieved may still be cytotoxic in vitro.

In a study involving four nonhuman primates, clofarabine demonstrated a median clearance rate of 17 mL/min/kg and a terminal half-life of 105 minutes, suggesting a relatively quick elimination from the body.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plasma and cerebrospinal fluid pharmacokinetics of clofarabine in nonhuman primates. Berg, SL., Bonate, PL., Nuchtern, JG., et al.[2018]

18F-clofarabine is safe for use in humans and can effectively measure dCK expression in tissues, which may help predict responses to certain cancer treatments.

In a study involving five healthy volunteers, the highest radiation exposure was observed in the urinary bladder, with an average effective dose of 5.1 mSv, indicating manageable safety levels for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway. Barrio, MJ., Spick, C., Radu, CG., et al.[2020]

Clofarabine is a second-generation anticancer drug that shows greater efficacy and higher oral bioavailability at low doses compared to similar drugs like cladribine and fludarabine.

The drug works by inducing cell apoptosis through the inhibition of key enzymes involved in DNA synthesis, and it may also enhance the expression of certain genes, contributing to its cytotoxic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine)--biochemical aspects of anticancer activity. Majda, K., Lubecka, K., Kaufman-Szymczyk, A., et al.[2018]

In a phase I/II trial involving 44 adults with acute myeloid leukemia, clofarabine combined with total body irradiation (TBI) resulted in a low 6-month relapse rate of 16%, meeting the study's primary efficacy goal while maintaining acceptable safety with minimal severe toxicities.

Patients treated with the clofarabine-TBI regimen experienced significantly lower overall mortality and disease progression compared to historical data from those treated with fludarabine, suggesting that clofarabine may offer a more effective treatment option for high-risk AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II multisite trial of optimally dosed clofarabine and low-dose TBI for hematopoietic cell transplantation in acute myeloid leukemia. Krakow, EF., Gyurkocza, B., Storer, BE., et al.[2021]

The study explored the use of 18F-labeled clofarabine ([18F]CFA) for PET imaging to assess tumor proliferation in hepatocellular carcinoma (HCC), using a woodchuck model to simulate human liver cancer.

While some modifiers tested increased liver background uptake of [18F]CFA, the application of cold clofarabine successfully reduced this background, suggesting that combining cold CFA with [18F]CFA could enhance imaging accuracy for liver cancers and warrants further clinical investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F] Clofarabine for PET Imaging of Hepatocellular Carcinoma. Sergeeva, O., Kepe, V., Zhang, Y., et al.[2020]

Clofarabine is a second-generation purine nucleoside analogue that effectively inhibits DNA polymerases and ribonucleotide reductase, leading to apoptosis in both cycling and non-cycling cells.

It was approved by the FDA in 2004 for treating pediatric patients with relapsed or refractory acute lymphoblastic leukemia after at least two prior chemotherapy regimens, demonstrating its efficacy in hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. Lech-Maranda, E., Korycka, A., Robak, T.[2019]

In a phase 1 study involving seven Japanese pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL), clofarabine was found to have a tolerable safety profile, with all patients experiencing at least one serious adverse event, including anemia and neutropenia.

Despite the safety and pharmacokinetics of clofarabine being consistent with previous studies, the treatment did not result in any complete or partial remissions, indicating that further research with larger patient groups is necessary to assess its efficacy in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan. Koh, K., Ogawa, C., Okamoto, Y., et al.[2018]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05065736

Using a PET Imaging Agent, 18F-Clofarabine (CFA), to ... This clinical trial will be testing whether 18F-Clofarabine (CFA) could be an imaging agent to measure this aspect of cancer metabolism. Detailed Description.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4839461/

[18F]CFA as a clinically translatable probe for PET imaging ... [18F]CFA PET may provide a useful companion biomarker for therapeutic interventions against cancer that include nucleoside analog prodrugs, dCK ...

3. trialx.com trialx.com/clinical-trials/listings/229129/using-a-pet-imaging-agent-18f-clofarabine-cfa-to-measure-deoxycytidine-kinase-activity-in-metastatic-cancer/

Using a PET Imaging Agent, 18F-Clofarabine (CFA), to ... This clinical trial will be testing whether 18F-Clofarabine (CFA) could be an imaging agent to measure this aspect of cancer metabolism.

4. jnm.snmjournals.org jnm.snmjournals.org/content/58/3/374

Human Biodistribution and Radiation Dosimetry of 18 F ... Conclusion: Our results hint that 18F-clofarabine can be used safely in humans to measure tissue dCK expression. Future studies will determine ...

5. clin.larvol.com clin.larvol.com/trial-detail/NCT05065736

Using a PET Imaging Agent, 18F-Clofarabine (CFA), to ... Correlate changes in CFA uptake with participant outcomes as measured by all cause mortality/overall survival (OS). up to 12 months after CFA PET. Adverse ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6896045/

[18F] Clofarabine for PET Imaging of Hepatocellular ... The data included 102 samples from 13 animals, with a total of 42 tumor samples and 60 non-tumor samples (GSM896624-GSM896725) [26]. The data obtained were from ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02888301

18F-Clofarabine PET/CT in Imaging Cancer Patients ... This clinical trial studies 18F-clofarabine positron emission tomography (PET)/computed tomography (CT) in imaging patients with cancer before and after ...