A Phase 1 Trial Of Safety And Initial Efficacy Of Vagal Nerve Blockade For Cancer-Induced Cachexia In Patients With Metastatic Pancreatic Adenocarcinoma

Primary Objective:

To determine the safety and tolerability of the OnVagus device in patients wearing it while receiving chemotherapy.

Secondary Objective:

To determine the rate of cachexia arrest, as defined by weight stabilization or gain

Exploratory Objectives:

To analyze the changes in chemokine (C-C motif) ligand 2 (CCL2), tumor necrosis factor α (TNFa), acetylcholine (ACh), Growth/differentiation factor 15 (GDF15), Lipocalin-2 (LCN2), and liver function tests (LFTs) while patients receive vagal blockade.

To determine the device's impact on progression-free survival (PFS) and overall survival (OS) between patients receiving vagal blockade.

Inclusion criteria

• Patients with metastatic pancreatic cancer.
• Must have adenocarcinoma component (presence of combined histology is acceptable, as long as adenocarcinoma is present).
• Weight loss from baseline of at least 5% (Baseline weight can be anytime from diagnosis onward).
• Must have a tissue-based confirmation of diagnosis available. Tissue does not need to be a metastasis; primary tumor or prior surgery are acceptable sources.
• Must have had progression of disease after one prior line of therapy in the metastatic setting.
• Must be receiving or plan to receive another line of therapy in the metastatic setting. o If therapy is being administered outside MD Anderson, the patient is still eligible for this trial. o Enrollment onto a therapeutic clinical trial as this second line therapy is not explicitly excluded.
• Must have triple ECG results available. Patients will be ineligible if they present: o Second- or third-degree block.

• Prolonged QT wave.
• Atrial fibrillation or flutter.
• Uncontrolled ventricular fibrillation or flutter.
• Premature ventricular contractions (PVC).

Exclusion criteria

Exclusion criteria

• History of cervical vagotomy on the right side of neck.
• Known structural abnormalities on the right side of neck, including but not limited to situs inversus, bulky R-neck lymphadenopathy, etc., that in the investigators' opinion would lead to inability to correctly place the device onto the vagus nerve.
• Implanted electrical device that passes through the neck (e.g.: cranial implant with battery pack in chest, and wires running through the neck).
• Metal implants in the neck, including the cervical spine.
• Recent (6 months or less) nerve block or botox injections to the head or neck.
• Pain specifically localized to the treatment area, the right side of the neck.
• Prior severe cerebrovascular disease (e.g., intracranial aneurysm, intracranial hemorrhage, stroke).
• Prior severe cardiac disease, including but not limited to coronary artery disease (CAD), prior myocardial infarction (MI), uncontrolled congestive heart failure (CHF).