Hyperbaric Radiation Sensitization of Head and Neck Cancers

NCT03843671 | Unknown Phase 2 DMC FDA Drug FDA Device

• 2 other identifiers: NBS2019-193840508
• Study Type: interventional
• Target: 400
• Locations: 2 countries
• Sites: 5

Brief Summary

There is reason to believe that hyperbaric oxygen administered immediately prior to radiotherapy will prove beneficial for this cancer type and stage. The basis for this hypothesis is a review of several decades of published work, the conclusion of a recent (2018) Cochrane Review, and results of a Phase I trial.

Conditions

Squamous Cell Carcinoma of the Head and Neck

Keywords

Hyperbaric oxygen; HNSCC; Radiotherapy; Chemotherapy

Outcome Measures

Primary Outcomes (2)

• Progression free survival

  Per blinded radiotherapy assessor

  Two years

• Relapse free survival

  Per blinded radiotherapy assessor

  Two years

Secondary Outcomes (6)

• Overall survival

  Two years

• Incidence of acute hyperbaric complications; ear/sinus barotrauma, oxygen toxicity, myopia, confinement anxiety

  At seven weeks from start of protocol, having completed 35 hyperbaric chamber exposures

• Incidence and degree of acute radiation toxicity

  At seven weeks from start of protocol, having completed 35 radiotherapy treatments

• Incidence and degree of late radiation tissue injury

  Two years

• Hyperbaric protocol and radiotherapy dosing protocol compliance

  Approximately 45 days after initiation of protocol

Study Arms (2)

Group 1

EXPERIMENTAL

Hyperbaric oxygen Hyperbaric chamber

Drug: Hyperbaric oxygen; Device: Hyperbaric chamber

Group 2

SHAM COMPARATOR

Sham for hyperbaric oxygen Hyperbaric chamber

Drug: Hyperbaric oxygen; Device: Hyperbaric chamber

Interventions

Hyperbaric oxygen DRUG

Hyperbaric oxygen therapy

Also known as: Hyperbaric chamber

Group 1; Group 2

Hyperbaric chamber DEVICE

Hyperbaric chamber

Group 1; Group 2

Eligibility Criteria

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

You may qualify if:

• Patients with histological or microscopic proof (from the primary tumor and/or lymph nodes) of invasive squamous cell carcinoma of the oral cavity, oropharynx or larynx (World Health Organization type 1).
• Stage III or IV disease, M0
• Non-surgical candidate; for reasons of health or age (except biopsy)
• Human Papillomavirus (P16) negative
• Life expectancy of at least 6 months and a Karnofsky performance status of ≥ 70
• Age ≥ 18 years
• No distant metastatic disease
• No clinically significant heart disease:
• No significant ventricular arrhythmia requiring medication with antiarrhythmic. No symptomatic coronary artery disease (angina). No myocardial infarction within the last 6 months. No second or third degree heart block or bundle branch block or clinically significant conduction system abnormality.
• Patients must sign a study-specific informed consent form

You may not qualify if:

• Histology other than squamous cell carcinoma
• Evidence of metastasis (below the clavicle or distant) by clinical or radiographic means
• History of prior invasive malignancy, unless at least 5 years without evidence of recurrence (tumor-specific restaging)
• Prior resection of the primary tumor or lymph node, unless un-operated N2-N3 nodal disease or primary tumor remaining, respectively.
• Prior chemotherapy for head and neck cancer or radiotherapy to the head and neck
• Prior treatment with Bleomycin
• Creatinine clearance: measured or estimated Glomerular Filtration Rate \<40 ml/min.
• Patients with simultaneous primaries
• Pregnancy
• Participating in a conflicting protocol
• Pulmonary pathologies (risk of decompression-induced pulmonary barotrauma)
• Current, untreated pneumothorax. Previous history of spontaneous pneumothorax. Previous history of intrathoracic surgery. History or evidence of pulmonary blebs or bullous lung disease. Clinically significant chronic obstructive pulmonary disease, associated with carbon dioxide retention, poorly controlled or associated with acute bronchospasm.
• Where the hyperbaric physician deems the patient to have an otherwise unacceptable risk for hyperbaric chamber exposure
• Claustrophobia

Sponsors & Collaborators

• National Baromedical Services: lead
• Mayo Clinic: collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• CISSS de Chaudière-Appalaches: collaborator
• Memorial Hermann Hospital: collaborator
• David Grant U.S. Air Force Medical Center: collaborator
• 59th Medical Wing: collaborator
• Prisma Health Richland Hospital: collaborator
• William Jennings Bryan Dorn VA Medical Center: collaborator

Study Sites (5)

The Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

Location

Wilford Hall Medical Facility

San Antonio, Texas, 78236, United States

Location

Hotel Dieu Hospital of Levis

Lévis, Quebec, G6V 3Z1, Canada

Location

Related Publications (25)

• GRAY LH. Radiobiologic basis of oxygen as a modifying factor in radiation therapy. Am J Roentgenol Radium Ther Nucl Med. 1961 May;85:803-15. No abstract available.

  PMID: 13708070 BACKGROUND

• GRAY LH, CONGER AD, EBERT M, HORNSEY S, SCOTT OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953 Dec;26(312):638-48. doi: 10.1259/0007-1285-26-312-638. No abstract available.

  PMID: 13106296 BACKGROUND

• GRAY LH. Oxygenation in radiotherapy. I. Radiobiological considerations. Br J Radiol. 1957 Aug;30(356):403-6. doi: 10.1259/0007-1285-30-356-403. No abstract available.

  PMID: 13446401 BACKGROUND

• CHURCHILL-DAVIDSON I, SANGER C, THOMLINSON RH. High-pressure oxygen and radiotherapy. Lancet. 1955 May 28;268(6874):1091-5. doi: 10.1016/s0140-6736(55)90589-4. No abstract available.

  PMID: 14382503 BACKGROUND

• CHURCHILL-DAVIDSON I, SANGER C, THOMLINSON RH. Oxygenation in radiotherapy. II. Clinical application. Br J Radiol. 1957 Aug;30(356):406-22. doi: 10.1259/0007-1285-30-356-406. No abstract available.

  PMID: 13446402 BACKGROUND

• EMERY EW, LUCAS BG, WILLIAMS KG. Technique of irradiation of conscious patients under increased oxygen pressure. Lancet. 1960 Jan 30;1(7118):248-50. doi: 10.1016/s0140-6736(60)90170-7. No abstract available.

  PMID: 13820164 BACKGROUND

• SANGER C. High pressure oxygen and radiation therapy. Am J Roentgenol Radium Ther Nucl Med. 1959 Mar;81(3):498-503. No abstract available.

  PMID: 13627317 BACKGROUND

• ATKINS HL, SEAMAN WB, JACOX HW, MATTEO RS. EXPERIENCE WITH HYPERBARIC OXYGENATION IN CLINICAL RADIOTHERAPY. Am J Roentgenol Radium Ther Nucl Med. 1965 Mar;93:651-63. No abstract available.

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• CATER DB, SCHOENIGER EL, WATKINSON DA. Effects on oxygen tension of tumours of breathing oxygen at high pressures. Lancet. 1962 Aug 25;2(7252):381-3. doi: 10.1016/s0140-6736(62)90233-7. No abstract available.

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• Evans JC. Metastasis following radiotherapy in hyperbaric oxygen. Radiology. 1969 Nov;93(5):1155-7. doi: 10.1148/93.5.1155. No abstract available.

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• Johnson RE, Kagan AR, Bryant TL. Hyperbaric oxygen effect on experimental tumor growth. Radiology. 1967 Apr;88(4):775-7. doi: 10.1148/88.4.775. No abstract available.

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• Kohshi K, Kinoshita Y, Terashima H, Konda N, Yokota A, Soejima T. Radiotherapy after hyperbaric oxygenation for malignant gliomas: a pilot study. J Cancer Res Clin Oncol. 1996;122(11):676-8. doi: 10.1007/BF01209031.

  PMID: 8898978 BACKGROUND

• Machin D, Stenning SP, Parmar MK, Fayers PM, Girling DJ, Stephens RJ, Stewart LA, Whaley JB. Thirty years of Medical Research Council randomized trials in solid tumours. Clin Oncol (R Coll Radiol). 1997;9(2):100-14. doi: 10.1016/s0936-6555(05)80448-0.

  PMID: 9135895 BACKGROUND

• Haffty BG, Hurley R, Peters LJ. Radiation therapy with hyperbaric oxygen at 4 atmospheres pressure in the management of squamous cell carcinoma of the head and neck: results of a randomized clinical trial. Cancer J Sci Am. 1999 Nov-Dec;5(6):341-7.

  PMID: 10606475 BACKGROUND

• Kohshi K, Kinoshita Y, Imada H, Kunugita N, Abe H, Terashima H, Tokui N, Uemura S. Effects of radiotherapy after hyperbaric oxygenation on malignant gliomas. Br J Cancer. 1999 Apr;80(1-2):236-41. doi: 10.1038/sj.bjc.6690345.

  PMID: 10390002 BACKGROUND

• Kinoshita Y, Kohshi K, Kunugita N, Tosaki T, Yokota A. Preservation of tumour oxygen after hyperbaric oxygenation monitored by magnetic resonance imaging. Br J Cancer. 2000 Jan;82(1):88-92. doi: 10.1054/bjoc.1999.0882.

  PMID: 10638972 BACKGROUND

• Beppu T, Kamada K, Yoshida Y, Arai H, Ogasawara K, Ogawa A. Change of oxygen pressure in glioblastoma tissue under various conditions. J Neurooncol. 2002 May;58(1):47-52. doi: 10.1023/a:1015832726054.

  PMID: 12160140 BACKGROUND

• Becker A, Kuhnt T, Liedtke H, Krivokuca A, Bloching M, Dunst J. Oxygenation measurements in head and neck cancers during hyperbaric oxygenation. Strahlenther Onkol. 2002 Feb;178(2):105-8. doi: 10.1007/s00066-002-0892-0.

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• Ogawa K, Yoshii Y, Inoue O, Toita T, Saito A, Kakinohana Y, Adachi G, Ishikawa Y, Kin S, Murayama S. Prospective trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas. Radiother Oncol. 2003 Apr;67(1):63-7. doi: 10.1016/s0167-8140(02)00406-1.

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• Beppu T, Kamada K, Nakamura R, Oikawa H, Takeda M, Fukuda T, Arai H, Ogasawara K, Ogawa A. A phase II study of radiotherapy after hyperbaric oxygenation combined with interferon-beta and nimustine hydrochloride to treat supratentorial malignant gliomas. J Neurooncol. 2003 Jan;61(2):161-70. doi: 10.1023/a:1022169107872.

  PMID: 12622455 BACKGROUND

• Ogawa K, Yoshii Y, Inoue O, Toita T, Saito A, Kakinohana Y, Adachi G, Iraha S, Tamaki W, Sugimoto K, Hyodo A, Murayama S. Phase II trial of radiotherapy after hyperbaric oxygenation with chemotherapy for high-grade gliomas. Br J Cancer. 2006 Oct 9;95(7):862-8. doi: 10.1038/sj.bjc.6603342. Epub 2006 Sep 5.

  PMID: 16953239 BACKGROUND

• Kohshi K, Yamamoto H, Nakahara A, Katoh T, Takagi M. Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas. J Neurooncol. 2007 May;82(3):297-303. doi: 10.1007/s11060-006-9283-1. Epub 2006 Nov 22.

  PMID: 17120158 BACKGROUND

• Bennett M, et al. Hyperbaric Oxygenation for Tumor Sensitization to Radiotherapy. In The Cochrane Library, Issue 1, 2006. Oxford: Update Software. 1-61.

  BACKGROUND

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• Hartford AC, Davis TH, Buckey JC, Foote RL, Sinesi MS, Williams BB, Fariss AK, Schaner PE, Claus PL, Okuno SH, Hussey JR, Clarke RE. Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study. Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):481-486. doi: 10.1016/j.ijrobp.2016.10.048. Epub 2016 Nov 15.

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MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Hyperbaric Oxygenation

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Oxygen Inhalation Therapy; Respiratory Therapy; Therapeutics

Study Officials

• Richard E Clarke

  National Baromedical Services

  STUDY CHAIR

• James R Hussey, PhD

  University of South Carolina School of Public Health

  PRINCIPAL INVESTIGATOR

• James Wells, MD

  Dorn Veterans Medical Center

  PRINCIPAL INVESTIGATOR

• Lindsie Cone, MD

  Prisma Health Richland Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Richard E Clarke

CONTACT

+1.803.434.7101; dick.clarke@palmettohealth.org

Lindsie Cone, MD

CONTACT

+1.803.434.7812; lindsie.Cone@uscmed.sc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Both groups compressed in a hyperbaric chamber. Patients will be unaware of the compression gas or degree of pressurization as references to each are obscured
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized sham-controlled, with allocation concealment and blinded patients and assessors

Study Record Dates

• First Submitted: February 4, 2019
• First Posted: February 18, 2019
• Study Start: July 1, 2019
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2024
• Last Updated: February 18, 2019

Record last verified: 2019-02

Locations

US (4); CA (1)