A Study of Deferoxamine (DFO) in People With Leptomeningeal Metastasis

Leptomeningeal Metastases Clinical Trial

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

Status Recruiting

Clinical Trial Summary

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 leptomeningeal metastasis from solid tumor cancer. The researchers will test different doses of DFO to find the highest dose that causes few or mild side effects. When the dose is found, they will test it in future participants to see whether DFO is a safe and effective treatment for people with leptomeningeal metastasis from non-small cell lung cancer (NSCLC). They are also doing this study to see how the body absorbs, distributes, gets rid of, and responds to DFO.

Clinical Trial Description

Phase 1a

During the phase 1a arm, the MTD and PK/PD data will be evaluated in patients with LM from any solid tumor malignancy in an accelerated dose escalation fashion, with conversion to a traditional 3 + 3 dose escalation scheme at either dosing cohort 5 or when alternative criteria is met [either 1 patient experiences a DLT or 2 patients experience any grade 2 or higher nervous system disorder toxicity (except headache)]. All patients will receive IT-DFO via Ommaya reservoir 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. DLTs and new grade 2 or higher nervous system toxicities will be assessed for the first 28 days of each cohort.

Patients will undergo PK/PD assessments at the time of C1-3 doses 1 and 2 (six dosing time points) to evaluate changes iron, DFO, and ferrioxamine concentrations in the blood and CSF at each dosing cohort.

The Principal Investigator will consider the MTD determined by the dose escalation, any cumulative or delayed CNS toxicities (if present), and PK/PD data of phase 1a when determining the RP2D of phase 1b.

Phase 1b

The phase 1b dose expansion will be determined by the RP2D of the phase 1a arm, and will be restricted to patients with NSCLC. All patients will receive IT-DFO via Ommaya reservoir 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.

Patients will undergo PK/PD assessments at the time of C1-3 doses 1 and 2 (six dosing time points) to evaluate changes iron, DFO, and ferrioxamine concentrations in the blood and CSF at each dosing cohort. PK/PD assessments will no longer be required after 5 patients in phase 1b have completed all six timepoints of completed analysis.

In addition to safety and PK/PD endpoints, patients in phase 1b will also be assessed for early efficacy endpoints. ;

Related Conditions & MeSH terms

• Leptomeningeal Metastases
• Meningeal Carcinomatosis
• Neoplasm Metastasis

• NCT number: NCT05184816
• Study type: Interventional
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Adrienne Boire, MD, PhD
• Phone: 646-888-3786
• Email: boirea@mskcc.org
• Status: Recruiting
• Phase: Phase 1
• Start date: December 22, 2021
• Completion date: December 2024