Oxygen Measurements in Subcutaneous Tumors by EPR Oximetry Using OxyChip

Study Overview
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Brief Summary
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Tumors with low oxygen levels are associated with poor prognosis and resistance to standard radiotherapy or systemic therapies. The ability to make repeated oxygen measurements in tumors could be used to help select the most effective treatment or the best timing to start therapies. The purpose of this study is to ascertain the safety and feasibility of using an implantable oxygen sensor, known as the OxyChip, to make oxygen measurements in tumors using EPR oximetry, a technique related to magnetic resonance imaging (MRI).

Detailed Description
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This is an early feasibility Phase I clinical trial for safety. The total enrollment for this study is 60 patients (30 per phase). The study is split in a phase IA (short duration of implantation with no other cancer therapy planned prior to excision) and a phase IB (duration of implantation for up to 52 weeks while receiving neoadjuvant radiation therapy or systemic therapy prior to surgical excision), as described below. The initial 6 patients will have the OxyChip placed for a short duration (up to 4 weeks) after which the OxyChip will be removed when the tumor mass is resected, prior to delivery of any further therapies. After the successful implantation, removal, and evaluation of the OxyChip in the first 6 Phase IA patients, enrollment will be opened to an additional 24 Phase IA patients and to 6 Phase IB patients who will either receive neoadjuvant radiotherapy or systemic therapy (chemotherapy, biologic therapy, or endocrine therapy) while the OxyChip is in place. After the successful implantation, removal, and evaluation of the OxyChip in the first 3 Phase IB patients receiving radiation therapy or systemic therapy, enrollment will be opened to an additional 24 Phase IB patients. Up to five oxygen measurements per week will be made during the course of radiation or systemic therapy. The OxyChips will be removed at surgery. Patients receiving radiation or systemic therapy will be evaluated at least weekly for assessment with respect to any adverse events for the primary objective and oximetry measurements will be taken periodically at least one day after implantation and up to its removal at the planned tumor excision to assess the secondary objective. Following resection, the tissue surrounding the OxyChip will be examined for any adverse events for the primary objective. For the exploratory objectives, the tissue will also be examined for biomarkers associated with hypoxia or growth.

Official Title
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A Single-Institutional, Phase 1 Trial of Repeated Oxygen Measurements in Subcutaneous Tumors by Electron Paramagnetic Resonance (EPR) Oximetry Using an Implantable Oxygen Sensor (OxyChip)

Conditions
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Neoplasms, Benign, Neoplasms, Malignant

Intervention / Treatment
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* Device: OxyChip


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase IA: Any tumor identified by imaging or physical exam to be accessable to OxyChip implantation and measurements and that is going to receive surgical resection with intent to remove the entire tumor. The tumor must be sufficiently large to accommodate the OxyChip. Phase IB: Any biopsy-proven malignancy expected to undergo neoadjuvant chemotherapy or radiotherapy prior to resection. The tumor must be sufficiently large to accommodate the OxyChip. The tumor must be within 3 cm of the surface of the skin or mucosa. Age ≥18 years old. Subject must be capable of giving informed consent. Anticipated time between implantation and planned surgical excision of at least three days. Tumors must be > 2.5 cm in minimum diameter to be eligible. Exclusion Criteria: Pregnant women or women of childbearing potential without adequate contraception. Contraception, which can include abstinence, is required from the first day of the last menstrual period until the removal of the OxyChip. Receipt of concurrent chemotherapy and radiotherapy, or planned sequential chemotherapy and radiotherapy, prior to resection (Phase IB), Receipt of Avastin, or other angiogenesis inhibitors, during the study. Prior radiotherapy to the site of implantation. Having other implanted (not removable) devices that generate electrical artifacts or that could be altered by the EPR magnetic field, such as cardiac pacemakers or defibrillators. Concurrent enrollment in any clinical research study, in the absence of cancer recurrence, in which the other study can reasonably be anticipated to have the potential for causing adverse events that would affect our primary endpoint of assessing the safety of the OxyChip device. If a study is not felt to impact the evaluation of adverse events in this trial then the patient will be eligible for concurrent enrollment. In the presence of confirmed clinical recurrence after initial cancer therapy (and after removal of OxyChip) during the year-long follow up stipulated in the protocol, patients will be eligible for all clinical trials as deemed appropriate by the treating oncologist. Patient platelet blood count < 50,000/l of blood, and absolute neutrophil count < 1,000/l of blood. Laboratory values must be obtained at least 3 months prior to implantation of the OxyChip.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There are two parallel arms of the study; however, the first 6 patients must be in the arm whose tumor will receive no therapy prior to surgical resection. If there are no safety issues, then both arms are open.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IA No treatment except standard-of-care (SOC) surgery<br>Placement of OxyChip will be through a minimally invasive procedure (needle injection) and removal will be at the time of surgical resection. In Phase IA, patients will not have any cancer therapy prior to removal of the OxyChip and duration of implantation is typically less than 4 weeks but may be up to 52 weeks. | Device: OxyChip<br>* The OxyChip is an investigational device to assess oxygen level in tissues, when measured with Electron Paramagnetic Resonance (EPR).<br>* Other names: implantable oxygen sensor;|
| Experimental: IB SOC adjuvant therapy and SOC surgery<br>Placement of OxyChip will be through a minimally invasive procedure (needle injection) and removal will be at the time of surgical resection. In Phase IB, patients will have standard of care neoadjuvant chemotherapy or pre-operative radiation therapy during the time that the OxyChip is within the tumor, which is typically 6 weeks but may be up to 52 weeks. | Device: OxyChip<br>* The OxyChip is an investigational device to assess oxygen level in tissues, when measured with Electron Paramagnetic Resonance (EPR).<br>* Other names: implantable oxygen sensor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of OxyChip by Recording of Adverse Events as Measured by Histological Signs of Tissue Reaction and Inflammation | This is a safety study to demonstrate that the OxyChip will be well-tolerated with minimal risk for complications. All tumors will be excised with the OxyChip in place, and histology will be analyzed for signs of tissue reaction and inflammation adjacent to the OxyChip. pathologic findings associated with the OxyChip are reported. | From time of implantation procedure to 2 weeks after removal of OxyChip, up to 18 weeks | 
| Safety of OxyChip by Recording of Adverse Events (Allergic Reaction, Infection, Hemorrhage, Skin Erosion Over the Device, Device Breakage or Malfunction) | This is a safety study to demonstrate that the implantation procedure, the OxyChip and any subsequent oxygen measurements will be well-tolerated with minimal risk for complications. | From time of implantation procedure to 2 weeks after removal of OxyChip | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of Tumor Partial Pressure of Oxygen (pO2) Levels Using the OxyChip Sensor and EPR Oximetry | This study will also determine the feasibility of repeated measurements of pO2 in tumors using the OxyChip and EPR oximetry. Tumor pO2 values will be reported in millimeters of mercury (mmHg). Two types of measurements (Data) were made: (i) Baseline tumor pO2 values in patients breathing room air during the first up to 10 min period; and (ii) Hyperoxygenation pO2 values at the end of patients breathing 100% oxygen gas for up to 10 min. The hyperoxygenation was administered immediately following the baseline (room-air breathing) measurements. | From time of implantation procedure to time of OxyChip removal; an average of 2 weeks for Phase IA and up to 4 months for Phase IB | 
| The Time Required to Complete EPR Oximetry Measurements | This study will also determine the feasibility of repeated measurements of oxygen in tumors using the OxyChip and EPR oximetry. We will determine the workflow and time required for each daily oxygen measurement. The measurement time, averaged over multiple measurements on each patient, will be reported as less than or greater than one hour. | From time of preparing the patient for EPR measurement, for example placement of the patient on the bed, attaching the resonator, to completion of the EPR measurements, for example, detaching the resonator and removing the patient off the bed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electron Paramagnetic Resonance, Hypoxia, OxyChip