35 Participants Needed

Deferoxamine for Meningeal Carcinomatosis

Recruiting at 14 trial locations
AB
JW
AB
Helena Yu, MD profile photo
Overseen ByHelena Yu, MD
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: Memorial Sloan Kettering Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether deferoxamine (DFO), administered directly into the cerebrospinal fluid (CSF), is a safe treatment for individuals with leptomeningeal metastasis, where cancer spreads to the membranes surrounding the brain and spinal cord. Researchers will test various doses to identify the safest one with minimal side effects. The trial targets those with leptomeningeal metastasis from solid tumors, whether newly diagnosed or persistent, who may benefit from additional treatment. Participants should have a functioning Ommaya reservoir (a device for delivering medication to the CSF) or be willing to have one placed. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot use systemic iron chelators within 4 weeks of the first dose or ascorbic acid or prochlorperazine within 2 weeks of the first dose. If you are on a systemic treatment controlling your extracranial disease, you may continue it during the study.

Is there any evidence suggesting that deferoxamine (DFO) is likely to be safe for humans?

Research has shown that deferoxamine (DFO) has been studied for safety when administered directly into the cerebrospinal fluid (CSF), the fluid surrounding the brain and spinal cord. This method is crucial for treating leptomeningeal metastasis, cancer that has spread to these areas. Since the 1970s, many studies have explored administering treatments like DFO directly into the CSF to find effective ways to treat cancers that spread to the brain and spinal cord.

Although specific data on DFO's safety in these studies is limited, its testing in human trials suggests researchers see potential in it. Early trials aim to find a safe dose and observe the body's response. Testing in humans typically indicates that earlier research has shown it might be safe enough to proceed. This trial is in its early stages, focusing on ensuring the treatment's safety and determining the right dose.12345

Why do researchers think this study treatment might be promising?

Deferoxamine (DFO) is unique because it targets leptomeningeal metastases (LM) with a new delivery method: intrathecal administration, which means it is delivered directly into the cerebrospinal fluid. This approach allows the drug to reach cancer cells more directly and effectively than traditional systemic treatments like chemotherapy, which can struggle to penetrate the central nervous system. Researchers are excited about DFO because its mechanism involves chelating iron, which is crucial for tumor growth, potentially slowing down or stopping the progression of cancer cells in the meninges.

What evidence suggests that deferoxamine might be an effective treatment for leptomeningeal metastasis?

Research suggests that deferoxamine (DFO), the treatment under study in this trial, might help treat leptomeningeal metastasis, a condition where cancer spreads to the protective layers around the brain and spinal cord. DFO removes extra iron from the body, potentially slowing cancer growth since cancer cells need iron to spread. Early findings indicate that reducing iron might help control tumors, but specific results for DFO in this condition remain under investigation. Although limited data exists on DFO's effectiveness, its mechanism shows promise for affecting tumor growth in the brain and spine area. Further studies will determine if DFO is truly effective for this purpose.12567

Who Is on the Research Team?

JW

Jessica Wilcox, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with leptomeningeal metastasis from solid tumors or NSCLC, who have a life expectancy of at least 8 weeks and can use effective contraception. They must be stable enough not to need immediate brain metastases treatment, able to handle an Ommaya reservoir (a device placed in the brain for drug delivery), and have normal CSF flow.

Inclusion Criteria

Life expectancy ≥ 8 weeks in the opinion of the Investigator
My cancer, including lung cancer, has spread to the lining of my brain or spinal cord.
My cancer has spread to my brain but is stable elsewhere.
See 9 more

Exclusion Criteria

I am on a treatment for my brain metastases that is currently working.
I have not had brain radiation within the last week.
I have not undergone whole-brain or craniospinal radiation therapy.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Treatment

Participants receive intrathecal deferoxamine (IT-DFO) via Ommaya reservoir in an accelerated dose escalation fashion, with conversion to a traditional 3 + 3 dose escalation scheme. Dosing is twice per week during cycle 1, once per week during cycle 2, and once every 2 weeks for subsequent cycles until LM progression, intolerable toxicity, or death.

Varies by cohort, assessed for 28 days per cohort
Twice per week during cycle 1, once per week during cycle 2, once every 2 weeks for subsequent cycles

Phase 1b Treatment

Participants receive IT-DFO at the recommended phase 2 dose (RP2D) determined from phase 1a. Dosing is twice per week during cycle 1, once per week during cycle 2, and once every 2 weeks for subsequent cycles until LM progression, intolerable toxicity, or death. Early efficacy endpoints are assessed.

Until progression, intolerable toxicity, or death
Twice per week during cycle 1, once per week during cycle 2, once every 2 weeks for subsequent cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Deferoxamine (DFO)
Trial Overview Researchers are testing Deferoxamine (DFO) given directly into the cerebrospinal fluid (CSF) to find a safe dose for treating leptomeningeal metastasis from solid tumor cancers. They aim to determine how DFO affects the body and its safety and effectiveness against non-small cell lung cancer-related metastasis.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Deferoxamine (DFO)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Center for Experimental Therapeutics

Collaborator

Trials
1
Recruited
40+

F.M. KIRBY FOUNDATION

Collaborator

Trials
1
Recruited
40+

Published Research Related to This Trial

Deferoxamine (DFO) effectively inhibits the proliferation of human myeloid leukemia cell lines (HL-60, HEL, U-937) in a dose-dependent manner, with significant effects observed at concentrations above 20 microM.
The antiproliferative effects of DFO are linked to a decrease in DNA synthesis, which can be reversed by adding iron salts, suggesting that DFO's mechanism of action involves iron chelation and its impact on cellular processes.
Antileukemic effects of deferoxamine on human myeloid leukemia cell lines.Becton, DL., Roberts, B.[2013]
Deferoxamine mesylate (DFO) significantly improved the tumor-to-blood ratio in 67Ga tumor imaging in tumor-bearing rats, particularly when administered 12 hours after the 67Ga injection.
In human studies, while DFO helped accelerate the excretion of 67Ga from the blood, it did not consistently enhance the quality of tumor images, indicating a complex relationship between DFO administration and imaging efficacy.
Deferoxamine mesylate enhancement of 67Ga tumor-to-blood ratios and tumor imaging.Koizumi, K., Tonami, N., Hisada, K.[2019]
In a study involving rats with acute myelogenous leukemia, treatment with deferoxamine (DFO), an iron chelator, did not significantly improve survival compared to untreated groups, indicating limited efficacy in vivo.
Even when using a high molecular weight polymeric conjugate of DFO designed for sustained drug levels, there was no major impact on survival, suggesting that achieving effective cytotoxic levels of DFO in this type of leukemia may not be feasible.
Failure to alter the course of acute myelogenous leukemia in the rat with subcutaneous deferoxamine.Blatt, J., Boegel, F., Hedlund, BE., et al.[2019]

Citations

NCT05184816 | A Study of Deferoxamine (DFO) in People ...The researchers are doing this study to find out whether deferoxamine (DFO) given intrathecally (directly into the CSF) is a safe treatment for people with ...
Cerebrospinal Fluid-Administered Therapies for ...Results & conclusion: Outcomes were not reported consistently. Survival, when reported, remained poor. Intrathecal therapies for LM remain a ...
Leptomeningeal Metastases: New Opportunities in the ...Importantly, treatment with pCSI was effective for both newly diagnosed and recurrent LM. Median overall survival (OS) was 8 months (95% CI: 6-NR) with a median ...
A Phase I Study of Deferoxamine in People ...Researchers think that the study drug, deferoxamine (DFO), may be an effective treatment for leptomeningeal metastases because it helps remove iron from the ...
Deferoxamine for Meningeal CarcinomatosisThis trial is testing whether injecting deferoxamine into the fluid around the brain and spinal cord is safe for people with cancer that has spread there.
Leptomeningeal Disease: Current Approaches and Future ...Safety and tolerability of proton CSI for patients with LMD from solid tumors was established in a phase I clinical trial [47]. In this study, ...
Leptomeningeal metastases from solid tumors: A Society for ...Intrathecal drug administration is generally most effective against floating and thin linear deposits of LM in patients with unobstructed CSF flow dynamics.
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