Testing Deferoxamine for Leptomeningeal Metastasis Treatment

A Phase 1a/1b Trial of Intrathecal Deferoxamine for Leptomeningeal Metastases

This study is testing if giving a drug called deferoxamine directly into the spinal fluid can safely help people with leptomeningeal metastasis from solid tumors.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: bevacizumab, ipilimumab, nivolumab, pembrolizumab, atezolizumab, erlotinib, osimertinib, lorlatinib, lapatinib, tucatinib, trametinib, cobimetinib, radiation, doxorubicin
• Locations: 7 sites (Basking Ridge, New Jersey and 6 other locations)
• Trial ID: NCT05184816 on ClinicalTrials.gov

What this trial studies

This study investigates the safety and dosage of deferoxamine (DFO) administered directly into the cerebrospinal fluid (CSF) for patients with leptomeningeal metastasis from solid tumors. It employs a phased approach, starting with a dose escalation to determine the maximum tolerated dose (MTD) and pharmacokinetics. Participants will receive DFO via an Ommaya reservoir, with treatment frequency decreasing over time, and will be monitored for side effects and efficacy. The study aims to establish a recommended phase 2 dose (RP2D) for further evaluation.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with leptomeningeal metastasis from any solid tumor malignancy.

Not a fit: Patients with leptomeningeal metastasis who have a poor performance status or life expectancy of less than 8 weeks may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from leptomeningeal metastasis.

How similar studies have performed: While the use of deferoxamine in this context is novel, similar studies targeting leptomeningeal metastasis have shown promise in exploring new treatment avenues.

Eligibility criteria

Inclusion Criteria:

* Age ≥ 18 years on the day of consenting to study
* ECOG performance status ≤ 2 or KPS ≥ 60.
* Life expectancy ≥ 8 weeks in the opinion of the Investigator
* LM from any solid tumor malignancy (1a and 1b), that is either:

  * Newly diagnosed: As evidenced by positive CSF cytology, CTC count \>3.0/3.0 mL, or unequivocal radiographic evidence of LM on contrast-enhanced MRI, OR
  * Recurrent: As evidenced by unequivocal radiographic progression on contrast-enhanced MRI, the development of newly or recurrently positive CSF cytology, or a clinically-relevant rise in CSF CTCs at the discretion of the treating Investigator. There are no restrictions on the number of recurrences.

OR

* Persistent: As evidenced by any detectable disease (abnormal leptomeningeal enhancement on contrast-enhanced MRI; positive, suspicious, or atypical cytology; positive CSF CTCs; extrinsic cells on CSF cell count differential; or clinical symptoms attributed to LM) after receiving LM-directed radiation or systemic therapy. This includes patients with stable or partially responding LM who, in the opinion of the investigator, would benefit from additional LM-directed therapy.

  * Confirmation of solid tumor malignancy (phase 1a and 1b) may be made by histopathologic criteria of any primary or metastatic site. For patients that have not previously undergone internal pathology review at MSKCC, a pathology report confirming the primary malignancy is sufficient.
  * Patients can have concomitant parenchymal brain metastases at study entry as long as they do not require active treatment or have been previously treated.
  * Patients with seizure disorders, stable on appropriate antiepileptic therapies, are eligible for this trial.
  * Patients must have normal CSF flow dynamics at the clinical judgment of the treating investigator, with no obstructive hydrocephalus or ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt.
  * Patients with isolated intracranial LM progression and stable extracranial disease may enroll on trial. If this population is receiving systemic treatment that is controlling their extracranial disease, they may remain on this regimen during study enrollment provided their LM progression occurred on this regimen.
  * For patients with both intracranial and extracranial disease progression at the time of study screening, necessitating change to their systemic tumor-directed therapy:
* If the new systemic treatment of choice has known CNS activity at the discretion of the Principal Investigator, then they should be monitored on this new regimen for 21 days with confirmation of persistent LM (by neuraxial imaging and CSF reassessment) before enrolling on study.
* If the new systemic treatment of choice has no known CNS activity at the discretion of the Principal Investigator, then they may start IT-DFO concurrently with the new systemic treatment.
* Examples of systemic CNS-active treatments include but are not limited to: bevacizumab, temozolomide, carmustine, lomustine, etoposide, carboplatin, cisplatin, pemetrexed, doxorubicin, high-dose erlotinib, osimertinib, lorlatinib, lapatinib, tucatinib, capecitabine, dabrafenib, trametinib, vemurafenib, cobimetinib, ipilimumab, nivolumab, pembrolizumab, atezolizumab

  * Patients must have a functioning Ommaya reservoir prior to the first IT-DFO administration or be an appropriate surgical candidate for Ommaya reservoir placement and agree to Ommaya reservoir placement as standard of care prior to the first IT-DFO administration.
  * Patients that have screening laboratory values out of range, but not clinically significant, may be considered eligible on a case by case basis deemed by the clinical investigator. Adequate bone marrow and organ function is demonstrated by:
* White blood cell (WBC) count ≥ 2.5 K/mcL or if this value is less, an exemption has been granted by the treating physician or primary investigator.
* Absolute neutrophil count (ANC) ≥ 1.0 K/mcL
* Platelet count ≥ 50 K/mcL at least 7 days from last platelet transfusion, or if this value is less, an exemption has been granted by the treating physician or primary investigator.
* Hemoglobin (Hgb) ≥ 8 g/dL, or if this value is less, an exemption has been granted by the treating physician or primary investigator.
* Serum creatinine ≤ 1.5 times the upper limit of normal (ULN) or if this value is more, an exemption has been granted by the treating physician or primary investigator.
* Serum bilirubin ≤ 1.5 times the ULN; or total bilirubin ≤ 3 times the ULN with direct bilirubin within the normal range in patients with well documented Gilbert Disease or if this value is more, an exemption has been granted by the treating physician or primary investigator.
* Serum alanine aminotransferase (ALT) and aspartate aminotransaminase (AST) ≤ 3 times the ULN, unless known hepatic disease wherein may be ≤ 5 times the ULN is acceptable. If this value is more, an exemption must be granted by the treating physician or primary investigator.

  * Women of child-bearing potential and sexually active males must commit to the use of effective contraception while on study.

Exclusion Criteria:

* Any CNS-directed irradiation within 7 days of first dose of IT-DFO.
* Patients receiving other therapy (either intrathecal or systemic) designed to treat their LM, with ongoing acceptable control of their LM.
* Any contraindication to gadolinium-enhanced MRI
* Use of any systemic iron chelators within 4 weeks of first dose
* Use of ascorbic acid or prochlorperazine within 2 weeks of first dose
* Patients are not allowed to receive whole-brain radiation therapy or craniospinal radiation therapy during study enrollment.
* Patients must not have any physical and/or psychiatric illness that would interfere with their compliance and ability to tolerate treatment as per the protocol.
* Women may not be pregnant or breastfeeding
* Known hypersensitivity orSpecial Characters

Where this trial is running

Basking Ridge, New Jersey and 6 other locations

• Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (Limited Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (Limited Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (Limited Protocol Activities) — Uniondale, New York, United States (Recruiting)

Study contacts

• Principal investigator: Jessica Wilcox, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Jessica Wilcox, MD

Conditions Leptomeningeal Metastases; Deferoxamine; 21-378; recurrent; persistent