Oxygen Measurements in Subcutaneous Tumors by EPR Oximetry Using OxyChip

NCT02706197 | Terminated Results DMC FDA Device

• 2 other identifiers: 28499 D14007P01CA190193
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Neoplasms, Benign; Neoplasms, Malignant

Keywords

Electron Paramagnetic Resonance; Hypoxia; OxyChip

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Measurement of Tumor Partial Pressure of Oxygen (pO2) Levels Using the OxyChip Sensor and EPR Oximetry

  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

  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.

Study Arms (2)

IA No treatment except standard-of-care (SOC) surgery

EXPERIMENTAL

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

IB SOC adjuvant therapy and SOC surgery

EXPERIMENTAL

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

Interventions

OxyChip DEVICE

The OxyChip is an investigational device to assess oxygen level in tissues, when measured with Electron Paramagnetic Resonance (EPR).

Also known as: implantable oxygen sensor

IA No treatment except standard-of-care (SOC) surgery; IB SOC adjuvant therapy and SOC surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Periannan Kuppusamy: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03766, United States

Location

Related Publications (19)

• Brizel DM, Dodge RK, Clough RW, Dewhirst MW. Oxygenation of head and neck cancer: changes during radiotherapy and impact on treatment outcome. Radiother Oncol. 1999 Nov;53(2):113-7. doi: 10.1016/s0167-8140(99)00102-4.

  PMID: 10665787 BACKGROUND

• Vaupel P, Thews O, Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol. 2001;18(4):243-59. doi: 10.1385/MO:18:4:243.

  PMID: 11918451 BACKGROUND

• Swartz HM, Walczak T. Developing in vivo EPR oximetry for clinical use. Adv Exp Med Biol. 1998;454:243-52. doi: 10.1007/978-1-4615-4863-8_29.

  PMID: 9889898 BACKGROUND

• Doll CM, Milosevic M, Pintilie M, Hill RP, Fyles AW. Estimating hypoxic status in human tumors: a simulation using Eppendorf oxygen probe data in cervical cancer patients. Int J Radiat Oncol Biol Phys. 2003 Apr 1;55(5):1239-46. doi: 10.1016/s0360-3016(02)04474-7.

  PMID: 12654433 BACKGROUND

• Gagel B, Piroth M, Pinkawa M, Reinartz P, Zimny M, Kaiser HJ, Stanzel S, Asadpour B, Demirel C, Hamacher K, Coenen HH, Scholbach T, Maneschi P, DiMartino E, Eble MJ. pO polarography, contrast enhanced color duplex sonography (CDS), [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography: validated methods for the evaluation of therapy-relevant tumor oxygenation or only bricks in the puzzle of tumor hypoxia? BMC Cancer. 2007 Jun 28;7:113. doi: 10.1186/1471-2407-7-113.

  PMID: 17598907 BACKGROUND

• Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 2007 Jun;26(2):225-39. doi: 10.1007/s10555-007-9055-1.

  PMID: 17440684 BACKGROUND

• Cosse JP, Michiels C. Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anticancer Agents Med Chem. 2008 Oct;8(7):790-7. doi: 10.2174/187152008785914798.

  PMID: 18855580 BACKGROUND

• Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D. Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev. 2003 Aug;29(4):297-307. doi: 10.1016/s0305-7372(03)00003-3.

  PMID: 12927570 BACKGROUND

• Tatum JL, Kelloff GJ, Gillies RJ, Arbeit JM, Brown JM, Chao KS, Chapman JD, Eckelman WC, Fyles AW, Giaccia AJ, Hill RP, Koch CJ, Krishna MC, Krohn KA, Lewis JS, Mason RP, Melillo G, Padhani AR, Powis G, Rajendran JG, Reba R, Robinson SP, Semenza GL, Swartz HM, Vaupel P, Yang D, Croft B, Hoffman J, Liu G, Stone H, Sullivan D. Hypoxia: importance in tumor biology, noninvasive measurement by imaging, and value of its measurement in the management of cancer therapy. Int J Radiat Biol. 2006 Oct;82(10):699-757. doi: 10.1080/09553000601002324.

  PMID: 17118889 BACKGROUND

• Vaupel P. Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. Oncologist. 2008;13 Suppl 3:21-6. doi: 10.1634/theoncologist.13-S3-21.

  PMID: 18458121 BACKGROUND

• Cardenas-Navia LI, Yu D, Braun RD, Brizel DM, Secomb TW, Dewhirst MW. Tumor-dependent kinetics of partial pressure of oxygen fluctuations during air and oxygen breathing. Cancer Res. 2004 Sep 1;64(17):6010-7. doi: 10.1158/0008-5472.CAN-03-0947.

  PMID: 15342381 BACKGROUND

• Cardenas-Navia LI, Mace D, Richardson RA, Wilson DF, Shan S, Dewhirst MW. The pervasive presence of fluctuating oxygenation in tumors. Cancer Res. 2008 Jul 15;68(14):5812-9. doi: 10.1158/0008-5472.CAN-07-6387.

  PMID: 18632635 BACKGROUND

• O'Hara JA, Blumenthal RD, Grinberg OY, Demidenko E, Grinberg S, Wilmot CM, Taylor AM, Goldenberg DM, Swartz HM. Response to radioimmunotherapy correlates with tumor pO2 measured by EPR oximetry in human tumor xenografts. Radiat Res. 2001 Mar;155(3):466-73. doi: 10.1667/0033-7587(2001)155[0466:rtrcwt]2.0.co;2.

  PMID: 11182798 BACKGROUND

• O'Hara JA, Goda F, Dunn JF, Swartz HM. Potential for EPR oximetry to guide treatment planning for tumors. Adv Exp Med Biol. 1997;411:233-42. doi: 10.1007/978-1-4615-5865-1_28. No abstract available.

  PMID: 9269432 BACKGROUND

• Pandian RP, Dolgos M, Marginean C, Woodward PM, Hammel PC, Manoharan PT, Kuppusamy P. Molecular packing and magnetic properties of lithium naphthalocyanine crystals: hollow channels enabling permeability and paramagnetic sensitivity to molecular oxygen. J Mater Chem. 2009;19(24):4138-4147. doi: 10.1039/b901886g.

  PMID: 19809598 BACKGROUND

• Pandian RP, Parinandi NL, Ilangovan G, Zweier JL, Kuppusamy P. Novel particulate spin probe for targeted determination of oxygen in cells and tissues. Free Radic Biol Med. 2003 Nov 1;35(9):1138-48. doi: 10.1016/s0891-5849(03)00496-9.

  PMID: 14572616 BACKGROUND

• Meenakshisundaram G, Eteshola E, Pandian RP, Bratasz A, Selvendiran K, Lee SC, Krishna MC, Swartz HM, Kuppusamy P. Oxygen sensitivity and biocompatibility of an implantable paramagnetic probe for repeated measurements of tissue oxygenation. Biomed Microdevices. 2009 Aug;11(4):817-26. doi: 10.1007/s10544-009-9298-4.

  PMID: 19319683 BACKGROUND

• Meenakshisundaram G, Pandian RP, Eteshola E, Lee SC, Kuppusamy P. A paramagnetic implant containing lithium naphthalocyanine microcrystals for high-resolution biological oximetry. J Magn Reson. 2010 Mar;203(1):185-9. doi: 10.1016/j.jmr.2009.11.016. Epub 2009 Nov 26.

  PMID: 20006529 BACKGROUND

• Schaner PE, Pettus JR, Flood AB, Williams BB, Jarvis LA, Chen EY, Pastel DA, Zuurbier RA, diFlorio-Alexander RM, Swartz HM, Kuppusamy P. OxyChip Implantation and Subsequent Electron Paramagnetic Resonance Oximetry in Human Tumors Is Safe and Feasible: First Experience in 24 Patients. Front Oncol. 2020 Oct 27;10:572060. doi: 10.3389/fonc.2020.572060. eCollection 2020.

  PMID: 33194670 DERIVED

MeSH Terms

Conditions

Neoplasms; Hypoxia

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Periannan (Kupps) Kuppusamy MS, PhD
• Organization: Program for Clinical Oximetry and Imaging Geisel School of Medicine & Dartmouth Health; Dartmouth College

Periannan.Kuppusamy@dartmouth.edu

603-646-5490

Study Officials

• Philip E Schaner, M.D., Ph.D.

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

• Periannan Kuppusamy, Ph.D.

  Dartmouth College

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Scientific Director

Model Details: 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.

Study Record Dates

• First Submitted: February 26, 2016
• First Posted: March 11, 2016
• Study Start: December 31, 2015
• Primary Completion: June 30, 2021
• Study Completion: June 30, 2022
• Last Updated: September 21, 2023
• Results First Posted: September 21, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)