Nancy Beatriz Gordon, MD from MD Anderson discusses an abstract from ASCO 2020 entitled A Phase I Trial Of Aerosol Gemcitabine For The Treatment Of Patients With Solid Tumors And Lung Metastases
Therapeutic effectiveness has been seen in pre-clinical trials of aerosol gemcitabine (GCB) in mice and dogs with osteosarcoma (OS) lung metastases. In adults with lung cancer, aerosol GCB administered once a week has been shown to be healthy. Direct delivery of GCB through inhalation to the lungs can result in higher concentrations of drugs in the tumor with fewer side effects. In order to determine the viability and safety of aerosol GCB treatment in patients > 12 years with solid tumors and lung metastases, we launched a Phase I study (2015-0720- NCT03093909).
Eligibility criteria: (1) Diagnosis of solid tumor with lung metastases, (2) readiness to comply with protocol treatment, (3) sufficient organ function, (4) age of patients > 12 and < 50 years, (5) good success status, (6) resolution of all acute toxic effects of any previous anti-cancer therapy, and (7) no radiotherapy within two weeks. Patients who have received systemic GCB previously are eligible. Objectives: To evaluate the maximum tolerated dosage (MTD) and toxicity of GCB aerosol, to assess the spillover drug into the circulation, and to assess the anti-tumor activity preliminarily. Correlative studies include influence of GCB on immune cell infiltration in the lung, autophagy, apoptosis, heat shock protein 27, proof of DNA strand breaks (gH2AX), and expression of human equilibrium nucleoside transporter-1.Aerosol GCB is administered twice a week in 28-day cycles via a breath-induced nebulizer. It will be examined at a maximum of 6 dosage levels; the starting dose is 0.75 mg / kg twice weekly. Patients will proceed for 12 cycles if there is no progressive disease or unacceptable treatment-related toxicity. For the first 2 dose levels, the analysis uses the accelerated titration approach and then the 3 + 3 template for the remaining dose levels. We will test the identified MTD in an expansion cohort of 14 patients with relapsed OS, after determining the MTD. Symptoms, pulse oximetry, and pulmonary function are measured prior to each nebulized dose using remote spirometry that allows raw numbers and flow-volume curves to be imported and transmitted via bluetooth to a patient-provided android tablet. The data is transmitted to a web portal and recorded in a web-based database (REDCap) compatible with HIPAA, which is open to the research team.
To date, 4 patients have been included in the research, and the accrual is continuing at dose level 3.
This study will include details on aerosol GCB 's feasibility and safety. If proved feasible and effective, it can potentially provide a novel approach to lung treatment of metastatic OS while mitigating systemic toxicity. Details on clinical trials: NCT03093909.