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

Trial Summary

What is the purpose of this trial?

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.

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 data supports the effectiveness of the drug 18F-Clofarabine for cancer treatment?

Clofarabine, a component of 18F-Clofarabine, has shown effectiveness in treating blood cancers like acute myeloid leukemia and acute lymphoblastic leukemia, and it has been approved for use in certain pediatric leukemia cases. Additionally, combining clofarabine with imaging techniques has shown promise in liver cancer studies, suggesting potential for broader cancer applications. ^{1 2 3 4 5}

Is 18F-Clofarabine safe for humans?

Clofarabine has been used in various studies for treating leukemia, showing some common side effects like low blood cell counts, nausea, and liver enzyme changes. Serious side effects were less common, but included conditions like capillary leak syndrome and liver issues. Overall, it has been considered to have an acceptable safety profile in heavily pretreated patients. ^{3 5 6 7 8}

How is the drug 18F-Clofarabine unique for cancer treatment?

18F-Clofarabine is unique because it is used as a PET imaging probe to measure the expression of a specific enzyme (deoxycytidine kinase) in tumors, which can help predict how well a tumor will respond to certain cancer drugs. This imaging approach is different from traditional treatments as it focuses on assessing the tumor's characteristics rather than directly treating the cancer. ^{1 2 3 9 10}

Research Team

Roberto Vargas, MD

Principal Investigator

Cleveland Clinic, Case Comprehensive Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Clofarabine: a new treatment option for patients with acute myeloid leukemia. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Plasma and cerebrospinal fluid pharmacokinetics of clofarabine in nonhuman primates. [2018]

4. Switzerland pubmed.ncbi.nlm.nih.gov

[18F] Clofarabine for PET Imaging of Hepatocellular Carcinoma. [2020]

5. United States 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. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Clofarabine: in pediatric patients with acute lymphoblastic leukemia. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

Phase 1 study of clofarabine in pediatric patients with relapsed/refractory acute lymphoblastic leukemia in Japan. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Haploidentical Donor Transplantation Using a Novel Clofarabine-containing Conditioning Regimen for Very High-risk Hematologic Malignant Neoplasms. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Human Biodistribution and Radiation Dosimetry of 18F-Clofarabine, a PET Probe Targeting the Deoxyribonucleoside Salvage Pathway. [2020]

10. Poland pubmed.ncbi.nlm.nih.gov

Clofarabine (2-chloro-2'-fluoro-2'-deoxyarabinosyladenine)--biochemical aspects of anticancer activity. [2018]