Neoplasms, MalignantNCT03321903
EPR Tumor Oximetry With CE India Ink
An observational study of Neoplasms, Malignant and Breast Neoplasm, run by Philip Schaner at 1 site in United States.
Trial summary
It has been well established that malignant tumors tend to have low levels of oxygen and that tumors with very low levels of oxygen are more resistant to radiotherapy and other treatments, such as chemotherapy and immunotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Malignant, Breast Neoplasm, Carcinoma, Basal Cell
- What is being tested?
- Carlo Erba Ink Injection and EPR Oximetry Measurement
- Type of treatment
- Injection or infusion, Medical device
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Aug 2017to 27 Oct 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cancer patients with eligible tumors within 5mm of the surface, or that will be receiving postsurgical radiation following the resection of eligible tumors.
Who may be able to join
- Subject must be capable of giving informed consent or has an acceptable surrogate capable of giving consent on behalf of the subject.
- Subject has an eligible tumor that is within 5 mm of the surface (either skin or mucosa) or has had a tumor removed with a tumor bed that is within 5 mm of the surface.
- Eligible tumors types:
- Intraoral tumors: squamous cell carcinoma (SCC), melanoma;
- Primary cutaneous tumors (including, but not limited to): SCC, basal cell carcinoma (BCC,) melanoma;
- Breast malignancies post surgery;
- Other tumors: any tumor within 5 mm of the surface and with planned radiation therapy.
Who cannot join
- Previous adverse reaction to a charcoal product e.g., a local hypersensitive response from a black tattoo or from ingestion of activated charcoal
- Previous adverse reaction to the suspending agent
- Subject has a pacemaker that is not known to be MRI compatible
- Subject has a non-removable implant or device with metal that is not known to be MRI compatible
- Subject is pregnant or has a likelihood for becoming pregnant during the basic study timeframe.
- Note: There is no known harm to the woman or her fetus from participating; this is precautionary only.
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03766
About this study
Official title: Tumor Oximetry Using Electron Paramagnetic Resonance (EPR) With India Ink (Using Carbon Particulates From Carlo Erba [CE])
It has been well established that malignant tumors tend to have low levels of oxygen and that tumors with very low levels of oxygen are more resistant to radiotherapy and other treatments, such as chemotherapy and immunotherapy. Previous attempts to improve response to therapy by increasing the oxygen level of tissues have had disappointing results and collectively have not led to changing clinical practice. Without a method to measure oxygen levels in tumors or the ability to monitor over time whether tumors are responding to methods to increase oxygen during therapy, clinician's reluctance to use oxygen therapy in usual practice is not surprising.
The hypothesis underlying this research is that repeated measurements of tissue oxygen levels can be used to optimize cancer therapy, including combined therapy, and to minimize normal tissue side effects or complications. Because studies have found that tumors vary both in their initial levels of oxygen and exhibit changing patterns during growth and treatment, we propose to monitor oxygen levels in tumors and their responsiveness to hyperoxygenation procedures. Such knowledge about oxygen levels in tumor tissues and their responsiveness to hyper-oxygenation could potentially be used to select subjects for particular types of treatment, or otherwise to adjust routine care for patients known to have hypoxic but unresponsive tumors in order to improve their outcomes.
The overall objectives of this study are to establish the clinical feasibility and efficacy of using in vivo electron paramagnetic resonance (EPR) oximetry-a technique related to magnetic resonance imaging (MRI)-to obtain direct and repeated measurements of clinically useful information about tumor tissue oxygenation in specific groups of subjects with the same types of tumors, and to establish the clinical feasibility and efficacy of using inhalation of enriched oxygen to gain additional clinically useful information about responsiveness of tumors to hyper-oxygenation. Two devices are used: a paramagnetic charcoal suspension (Carlo Erba India ink) and in vivo EPR oximetry to assess oxygen levels. The ink is injected and becomes permanent in the tissue at the site of injection unless removed; thereafter, the in vivo oximetry measurements are noninvasive and can be repeated indefinitely.
Read the detailed description
The study design uses consecutively enrolled patients. Patients can participate as long as they are willing, fit the criteria for being assigned to a cohort, and the India ink spot remains measurable by EPR. Patients whose ink spot is resected during usual care and who do not have or are not willing to obtain additional injections will be withdrawn. Otherwise, patients can be re-measured using the previously injected ink at any time during the course of the study.
The study is split into four cohorts, with a minimum of 1-5 patients expected to be enrolled annually in each cohort, and a total of approximately 10 subjects expected for each cohort. The cohorts are defined by the type of tumor and by scenarios when our measurements will be made relative to the patient's standard therapies: 1) intraoral tumors with planned resection and adjuvant radiation therapy; 2) cutaneous malignant tumors receiving surgical resection only, receiving radiation therapy only, or receiving both surgical resection and adjuvant radiation therapy; 3) breast tumor receiving radiation therapy following surgery; and 4) other tumors receiving radiation therapy. The diagnosis for patients in all cases assumes that an eligible tumor (or the postsurgical area receiving radiation) occurs within approximately one-half centimeter of the surface, as determined by physical exam or imaging if available. All potentially eligible subjects are approached by their treating physician; those who agree to be contacted and are subsequently consented are assigned to the cohort for which they qualify. There is no randomization and no stratification within the cohorts.
Our interest in in situ tumor oxygenation relates to the clinical need to measure oxygen in tumors prior to therapy, to understand tumor oxygen dynamics over the course of therapy, and to assess the effectiveness of oxygen modulation therapy during treatment. Our interest in the postsurgical radiation field relates to the clinical need to understand whether the temporal dynamics of oxygen within the postsurgical radiation field has the potential to enhance the effectiveness of adjuvant therapies, and to understand how changes in short and long term oxygenation within the postsurgical radiation field may facilitate diminishment of late side effects from surgery and/or radiotherapy.
Following enrollment in the study, each subject will receive an initial placement of one or more geographically separate injections of India ink into the tissue of interest (i.e., tumor and/or tumor bed and/or adjacent tissue) using the established procedures for the injection of the ink. The subject is expected to agree to periodic measurements of all injection sites (unless the ink injection has been surgically removed); the subject will be told to expect six or more visits for measurements during treatment, but must agree to have at least one measurement per injection site. Each measurement will typically consist of 3 ten minute consecutive periods during which the subject initially breathes room air, then 100% oxygen delivered through a non-rebreather face mask followed by a period breathing room air.
Patients will be evaluated during clinical and oximetry appointments with respect to the presence of any adverse events.
- Conditions
- Neoplasms, Malignant, Breast Neoplasm, Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Melanoma, Skin Neoplasm
- Being tested
- Carlo Erba Ink Injection, EPR Oximetry Measurement
- Keywords
- Oxygen, Oximetry, Electron Spin Resonance Spectroscopy, Carbon, Charcoal, Radiotherapy, India Ink, EPR, ESR, Immunotherapy
- Medical subject headings
- Neoplasms, Breast Neoplasms, Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Melanoma, Skin Neoplasms, Head and Neck Neoplasms, Anthrax
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carlo Erba Ink InjectionDevice
Also called Carbon particulate suspension, Charcoal suspension
Carlo Erba India ink is used in this study as a paramagnetic oxygen sensor that is injected into tissue, and which, when measured using EPR Oximetry, can provide sensitive, repeated, and direct measurements of tissue oxygen. Each study participant will receive at least one ink injection of 20-50µL of Carlo Erba India Ink. The ink injection will occur within 5mm of the body surface (i.e., skin or mucosa), and may be injected into tumor, postsurgical field of radiation, and/or adjacent normal tissue. Carlo Erba Ink is an aqueous suspension composed of charcoal powder, water for injection, and a suspending agent. Carlo Erba is the name of the manufacturer that supplies the charcoal.
EPR Oximetry MeasurementOther
Also called Oxygen measurement, oximetry measurement
An oximetry measurement visit consists of ~ 30 minutes of continuous scans of tissue oxygen in vivo, using an oxygen sensor (i.e., India ink) injected into the tumor that is noninvasively scanned using EPR oximetry. Scans, converted into measurements of pO2, characterize the current tumor oxygen level at: (1) 'steady state' (while breathing room air), 2) response to hyperoxygenation therapy (inhaling oxygen-enriched air for 10 min), and 3) response to resuming inhaling room air. EPR measurements are repeated noninvasively throughout radiation or chemotherapy, to examine changes. The minimum number of visits depends on the patient's cohort; all may have additional measurements. If the ink injection is not surgically removed, EPR oximetry measurements can be repeated indefinitely.
| Study group | Role | What they receive |
|---|---|---|
| 1: Intraoral Squamous Cell Carcinomas | Intraoral squamous cell carcinomas that are resected and receive adjuvant radiation therapy. These patients may receive a Carlo Erba Ink injection before surgical tumor resection, after tumor resection (in the postsurgical radiation field), or in both instances. Patients whose tumor is within 5 mm of the surface will have injections of India ink into the tumor itself and measurements made in the tumor prior to surgery. Patients whose tumor is deeper than 5 mm of the surface could participate only in the measurements of the postsurgical radiation field. EPR Oximetry measurements will be made in the tumor and/or, if applicable, over the course of radiation in the postsurgical radiation field as appropriate. Receives: Device: Carlo Erba Ink Injection; Other: EPR Oximetry Measurement | |
| 2: Cutaneous Malignant Tumors | Patients with primary cutaneous malignant tumors (including but not limited to squamous cell carcinoma, basal cell carcinoma, or melanoma) whose tumor is within 5 mm of the surface and whose treatment plan includes surgical resection and/or postsurgical radiation therapy. These patients may receive a Carlo Erba Ink injection before surgical tumor resection, after tumor resection (in the postsurgical radiation field), in both the tumor and the postsurgical radiation field, or in the tumor prior to radiation therapy. EPR Oximetry measurements will be made in the tumor and/or, if applicable, over the course of radiation in the tumor or postsurgical radiation field as appropriate. Receives: Device: Carlo Erba Ink Injection; Other: EPR Oximetry Measurement | |
| 3: Breast Cancers | Breast cancer patients whose treatment plan includes surgical resection followed by radiation therapy. All patients who receive a surgical resection will receive a Carlo Erba Ink injection in the radiation field after sufficient healing has occurred to the area to be injected, as determined in consultation with the treating physicians, and using topical anesthetic or local anesthetic, if the patient so desires. All patients in this cohort will be expected to agree to a minimum of one EPR Oximetry measurement in the planned radiation field prior to radiation and a minimum of one measurement made over the course of radiation therapy. Receives: Device: Carlo Erba Ink Injection; Other: EPR Oximetry Measurement | |
| 4: Other tumors | Other tumors within 5 mm of the surface, whose planned treatment includes radiotherapy of the tumor and does not include a planned resection of the tumor. As these other qualifying malignancies are expected to occur only rarely, they will be grouped into a single cohort despite potential varied histology. These patients will receive a Carlo Erba Ink injection in their tumor prior to radiation therapy. All patients in this cohort will be expected to agree to a minimum of one EPR Oximetry measurement in the planned radiation field prior to radiation and a minimum of one measurement made over the course of radiation therapy. Receives: Device: Carlo Erba Ink Injection; Other: EPR Oximetry Measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of oxygen levels in tissues in response to hyperoxic therapy
This study will assess whether the addition of hyperoxic therapy (100% oxygen delivered through a non-rebreather face mask) will increase the oxygen level of a tumor or tumor bed by > 5 mm Hg using EPR oximetry. Tumor oxygen values will be reported in millimeters of mercury (mmHg).
Measured: From time of ink injection to the time the ink is removed through surgical resection. This can range from days to years, or until the study's completion of enrollment, anticipated in 2020.
Secondary outcomes (4)
Characterize oxygen changes in tumor beds throughout the course of radiation therapy
This outcome will measure oxygen in the post-surgical tissue throughout the course of radiation therapy using EPR oximetry. Tissue oxygen values will be reported in millimeters of mercury (mmHg).
Measured: From time of ink injection through the completion of radiation therapy; an average of 4 months.
Characterize oxygen changes in tumors throughout the course of radiation therapy
This outcome will measure tumor tissue oxygen throughout the course of radiation therapy using EPR oximetry. Tissue oxygen values will be reported in millimeters of mercury (mmHg).
Measured: From time of ink injection through the completion of radiation therapy; an average of 4 months.
Characterize oxygen changes in tumor and tumor beds prior to radiation therapy
For those subjects receiving India ink injections in both the untreated tumor and in the post-surgical bed prior to radiation, we will examine patterns across these two 'states' in individual tumors, which can enhance our understanding of the relationship between the oxygen levels in the tumor and in the resulting tumor bed. Tissue oxygen values will be reported in millimeters of mercury (mmHg).
Measured: From time of ink injection through the completion of medical treatment for cancer; an average of 4 months.
Characterize oxygen changes in tumor and tumor beds through the course of radiation therapy
For those subjects receiving India ink injections in both the untreated tumor and in the post-surgical bed while undergoing radiation therapy, we will examine patterns across these two 'states' in individual tumors, which can enhance our understanding of the relationship between the oxygen levels in the tumor and in the resulting tumor bed. Tissue oxygen values will be reported in millimeters of mercury (mmHg).
Measured: From time of ink injection through the completion of medical treatment for cancer; an average of 6 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2017
- Study start30 Aug 2017
- Primary completion27 Oct 2019
- Study completion27 Oct 2019
Why it stopped: The research team is exploring device optimization
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (71)Papers the sponsor has linked to this study.
- Other trials for Neoplasms, MalignantStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philip Schaner
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Philip Schaner, Dartmouth-Hitchcock Medical Center
- Investigators
- Philip E Schaner, M.D., Ph.D., Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03321903
- Sponsor's protocol ID
- 29880 D17008
- Other IDs
- P01CA190193
- Status last verified
- Dec 2019
- First submitted
- 20 Oct 2017
- Last updated
- 19 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Bacic G, Liu KJ, O'Hara JA, Harris RD, Szybinski K, Goda F, Swartz HM. Oxygen tension in a murine tumor: a combined EPR and MRI study. Magn Reson Med. 1993 Nov;30(5):568-72. doi: 10.1002/mrm.1910300507.
PubMed 8259056Baudelet C, Gallez B. How does blood oxygen level-dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors? Magn Reson Med. 2002 Dec;48(6):980-6. doi: 10.1002/mrm.10318.
PubMed 12465107Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Dodge RK, Charles HC, Samulski TV, Prosnitz LR, Dewhirst MW. Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. Cancer Res. 1996 Dec 1;56(23):5347-50.
PubMed 8968082Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285-9. doi: 10.1016/s0360-3016(97)00101-6.
PubMed 9226314Charlier N, Beghein N, Gallez B. Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR. NMR Biomed. 2004 Aug;17(5):303-10. doi: 10.1002/nbm.902.
PubMed 15366029Chaplin DJ, Horsman MR. Tumor blood flow changes induced by chemical modifiers of radiation response. Int J Radiat Oncol Biol Phys. 1992;22(3):459-62. doi: 10.1016/0360-3016(92)90853-a.
PubMed 1735678Dardzinski BJ, Sotak CH. Rapid tissue oxygen tension mapping using 19F inversion-recovery echo-planar imaging of perfluoro-15-crown-5-ether. Magn Reson Med. 1994 Jul;32(1):88-97. doi: 10.1002/mrm.1910320112.
PubMed 8084241Demidenko E. Mixed models: theory and applications with R. John Wiley & Sons; 2013 Aug 26.
Dewhirst MW, Poulson JM, Yu D, Sanders L, Lora-Michiels M, Vujaskovic Z, Jones EL, Samulski TV, Powers BE, Brizel DM, Prosnitz LR, Charles HC. Relation between pO2, 31P magnetic resonance spectroscopy parameters and treatment outcome in patients with high-grade soft tissue sarcomas treated with thermoradiotherapy. Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):480-91. doi: 10.1016/j.ijrobp.2004.06.211.
PubMed 15667971Dunn JF, Ding S, O'Hara JA, Liu KJ, Rhodes E, Weaver JB, Swartz HM. The apparent diffusion constant measured by MRI correlates with pO2 in a RIF-1 tumor. Magn Reson Med. 1995 Oct;34(4):515-9. doi: 10.1002/mrm.1910340405.
PubMed 8524017Flood AB, Satinsky VA, Swartz HM. Comparing the Effectiveness of Methods to Measure Oxygen in Tissues for Prognosis and Treatment of Cancer. Adv Exp Med Biol. 2016;923:113-120. doi: 10.1007/978-3-319-38810-6_15.
PubMed 27526132Gallez B, Baudelet C, Jordan BF. Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications. NMR Biomed. 2004 Aug;17(5):240-62. doi: 10.1002/nbm.900.
PubMed 15366026Gallez B, Debuyst R, Dejehet F, Liu KJ, Walczak T, Goda F, Demeure R, Taper H, Swartz HM. Small particles of fusinite and carbohydrate chars coated with aqueous soluble polymers: preparation and applications for in vivo EPR oximetry. Magn Reson Med. 1998 Jul;40(1):152-9. doi: 10.1002/mrm.1910400120.
PubMed 9660565Gallez B, Swartz HM. In vivo EPR: when, how and why? NMR Biomed. 2004 Aug;17(5):223-5. doi: 10.1002/nbm.913.
PubMed 15366024Gatenby RA, Kessler HB, Rosenblum JS, Coia LR, Moldofsky PJ, Hartz WH, Broder GJ. Oxygen distribution in squamous cell carcinoma metastases and its relationship to outcome of radiation therapy. Int J Radiat Oncol Biol Phys. 1988 May;14(5):831-8. doi: 10.1016/0360-3016(88)90002-8.
PubMed 3360652
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tumor Oximetry Using Electron Paramagnetic Resonance (EPR) With India Ink (Using Carbon Particulates From Carlo Erba [CE])
- ClinicalTrials.gov ID
- NCT03321903
- Acronym / sponsor ID
- 29880 D17008
- Conditions
- Neoplasms, Malignant, Breast Neoplasm, Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Melanoma, Skin Neoplasm
- Keywords
- Oxygen, Oximetry, Electron Spin Resonance Spectroscopy, Carbon, Charcoal, Radiotherapy, India Ink, EPR
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: The research team is exploring device optimization
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Philip SchanerUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 30 Aug 2017 (actual)
- Primary completion
- 27 Oct 2019 (actual)
- Study completion
- 27 Oct 2019 (actual)
- First posted
- 26 Oct 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
It has been well established that malignant tumors tend to have low levels of oxygen and that tumors with very low levels of oxygen are more resistant to radiotherapy and other treatments, such as chemotherapy and immunotherapy. Previous attempts to improve response to therapy by increasing the oxygen level of tissues have had disappointing results and collectively have not led to changing clinical practice. Without a method to measure oxygen levels in tumors or the ability to monitor over time whether tumors are responding to methods to increase oxygen during therapy, clinician's reluctance to use oxygen therapy in usual practice is not surprising.
The hypothesis underlying this research is that repeated measurements of tissue oxygen levels can be used to optimize cancer therapy, including combined therapy, and to minimize normal tissue side effects or complications. Because studies have found that tumors vary both in their initial levels of oxygen and exhibit changing patterns during growth and treatment, we propose to monitor oxygen levels in tumors and their responsiveness to hyperoxygenation procedures. Such knowledge about oxygen levels in tumor tissues and their responsiveness to hyper-oxygenation could potentially be used to select subjects for particular types of treatment, or otherwise to adjust routine care for patients known to have hypoxic but unresponsive tumors in order to improve their outcomes.
The overall objectives of this study are to establish the clinical feasibility and efficacy of using in vivo electron paramagnetic resonance (EPR) oximetry-a technique related to magnetic resonance imaging (MRI)-to obtain direct and repeated measurements of clinically useful information about tumor tissue oxygenation in specific groups of subjects with the same types of tumors, and to establish the clinical feasibility and efficacy of using inhalation of enriched oxygen to gain additional clinically useful information about responsiveness of tumors to hyper-oxygenation. Two devices are used: a paramagnetic charcoal suspension (Carlo Erba India ink) and in vivo EPR oximetry to assess oxygen levels. The ink is injected and becomes permanent in the tissue at the site of injection unless removed; thereafter, the in vivo oximetry measurements are noninvasive and can be repeated indefinitely.
Detailed description
The study design uses consecutively enrolled patients. Patients can participate as long as they are willing, fit the criteria for being assigned to a cohort, and the India ink spot remains measurable by EPR. Patients whose ink spot is resected during usual care and who do not have or are not willing to obtain additional injections will be withdrawn. Otherwise, patients can be re-measured using the previously injected ink at any time during the course of the study.
The study is split into four cohorts, with a minimum of 1-5 patients expected to be enrolled annually in each cohort, and a total of approximately 10 subjects expected for each cohort. The cohorts are defined by the type of tumor and by scenarios when our measurements will be made relative to the patient's standard therapies: 1) intraoral tumors with planned resection and adjuvant radiation therapy; 2) cutaneous malignant tumors receiving surgical resection only, receiving radiation therapy only, or receiving both surgical resection and adjuvant radiation therapy; 3) breast tumor receiving radiation therapy following surgery; and 4) other tumors receiving radiation therapy. The diagnosis for patients in all cases assumes that an eligible tumor (or the postsurgical area receiving radiation) occurs within approximately one-half centimeter of the surface, as determined by physical exam or imaging if available. All potentially eligible subjects are approached by their treating physician; those who agree to be contacted and are subsequently consented are assigned to the cohort for which they qualify. There is no randomization and no stratification within the cohorts.
Our interest in in situ tumor oxygenation relates to the clinical need to measure oxygen in tumors prior to therapy, to understand tumor oxygen dynamics over the course of therapy, and to assess the effectiveness of oxygen modulation therapy during treatment. Our interest in the postsurgical radiation field relates to the clinical need to understand whether the temporal dynamics of oxygen within the postsurgical radiation field has the potential to enhance the effectiveness of adjuvant therapies, and to understand how changes in short and long term oxygenation within the postsurgical radiation field may facilitate diminishment of late side effects from surgery and/or radiotherapy.
Following enrollment in the study, each subject will receive an initial placement of one or more geographically separate injections of India ink into the tissue of interest (i.e., tumor and/or tumor bed and/or adjacent tissue) using the established procedures for the injection of the ink. The subject is expected to agree to periodic measurements of all injection sites (unless the ink injection has been surgically removed); the subject will be told to expect six or more visits for measurements during treatment, but must agree to have at least one measurement per injection site. Each measurement will typically consist of 3 ten minute consecutive periods during which the subject initially breathes room air, then 100% oxygen delivered through a non-rebreather face mask followed by a period breathing room air.
Patients will be evaluated during clinical and oximetry appointments with respect to the presence of any adverse events.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 1: Intraoral Squamous Cell Carcinomas | – | Device: Carlo Erba Ink Injection, Other: EPR Oximetry MeasurementIntraoral squamous cell carcinomas that are resected and receive adjuvant radiation therapy. These patients may receive a Carlo Erba Ink injection before surgical tumor resection, after tumor resection (in the postsurgical radiation field), or in both instances. Patients whose tumor is within 5 mm of the surface will have injections of India ink into the tumor itself and measurements made in the tumor prior to surgery. Patients whose tumor is deeper than 5 mm of the surface could participate only in the measurements of the postsurgical radiation field. EPR Oximetry measurements will be made in the tumor and/or, if applicable, over the course of radiation in the postsurgical radiation field as appropriate. |
| 2: Cutaneous Malignant Tumors | – | Device: Carlo Erba Ink Injection, Other: EPR Oximetry MeasurementPatients with primary cutaneous malignant tumors (including but not limited to squamous cell carcinoma, basal cell carcinoma, or melanoma) whose tumor is within 5 mm of the surface and whose treatment plan includes surgical resection and/or postsurgical radiation therapy. These patients may receive a Carlo Erba Ink injection before surgical tumor resection, after tumor resection (in the postsurgical radiation field), in both the tumor and the postsurgical radiation field, or in the tumor prior to radiation therapy. EPR Oximetry measurements will be made in the tumor and/or, if applicable, over the course of radiation in the tumor or postsurgical radiation field as appropriate. |
| 3: Breast Cancers | – | Device: Carlo Erba Ink Injection, Other: EPR Oximetry MeasurementBreast cancer patients whose treatment plan includes surgical resection followed by radiation therapy. All patients who receive a surgical resection will receive a Carlo Erba Ink injection in the radiation field after sufficient healing has occurred to the area to be injected, as determined in consultation with the treating physicians, and using topical anesthetic or local anesthetic, if the patient so desires. All patients in this cohort will be expected to agree to a minimum of one EPR Oximetry measurement in the planned radiation field prior to radiation and a minimum of one measurement made over the course of radiation therapy. |
| 4: Other tumors | – | Device: Carlo Erba Ink Injection, Other: EPR Oximetry MeasurementOther tumors within 5 mm of the surface, whose planned treatment includes radiotherapy of the tumor and does not include a planned resection of the tumor. As these other qualifying malignancies are expected to occur only rarely, they will be grouped into a single cohort despite potential varied histology. These patients will receive a Carlo Erba Ink injection in their tumor prior to radiation therapy. All patients in this cohort will be expected to agree to a minimum of one EPR Oximetry measurement in the planned radiation field prior to radiation and a minimum of one measurement made over the course of radiation therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cancer patients with eligible tumors within 5mm of the surface, or that will be receiving postsurgical radiation following the resection of eligible tumors.
Key inclusion criteria (7 listed)
- Subject must be capable of giving informed consent or has an acceptable surrogate capable of giving consent on behalf of the subject.
- Subject has an eligible tumor that is within 5 mm of the surface (either skin or mucosa) or has had a tumor removed with a tumor bed that is within 5 mm of the surface.
Key exclusion criteria (6 listed)
- Previous adverse reaction to a charcoal product e.g., a local hypersensitive response from a black tattoo or from ingestion of activated charcoal
- Previous adverse reaction to the suspending agent
- Subject has a pacemaker that is not known to be MRI compatible
- Subject has a non-removable implant or device with metal that is not known to be MRI compatible
- Subject is pregnant or has a likelihood for becoming pregnant during the basic study timeframe.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carlo Erba Ink InjectionAlso: Carbon particulate suspension, Charcoal suspensionCarlo Erba India ink is used in this study as a paramagnetic oxygen sensor that is injected into tissue, and which, when measured using EPR Oximetry, can provide sensitive, repeated, and direct measurements of tissue oxygen. Each study participant will receive at least one ink injection of 20-50µL of Carlo Erba India Ink. The ink injection will occur within 5mm of the body surface (i.e., skin or mucosa), and may be injected into tumor, postsurgical field of radiation, and/or adjacent normal tissue. Carlo Erba Ink is an aqueous suspension composed of charcoal powder, water for injection, and a suspending agent. Carlo Erba is the name of the manufacturer that supplies the charcoal. | Device | 1: Intraoral Squamous Cell Carcinomas, 2: Cutaneous Malignant Tumors, 3: Breast Cancers, 4: Other tumors |
| EPR Oximetry MeasurementAlso: Oxygen measurement, oximetry measurementAn oximetry measurement visit consists of ~ 30 minutes of continuous scans of tissue oxygen in vivo, using an oxygen sensor (i.e., India ink) injected into the tumor that is noninvasively scanned using EPR oximetry. Scans, converted into measurements of pO2, characterize the current tumor oxygen level at: (1) 'steady state' (while breathing room air), 2) response to hyperoxygenation therapy (inhaling oxygen-enriched air for 10 min), and 3) response to resuming inhaling room air. EPR measurements are repeated noninvasively throughout radiation or chemotherapy, to examine changes. The minimum number of visits depends on the patient's cohort; all may have additional measurements. If the ink injection is not surgically removed, EPR oximetry measurements can be repeated indefinitely. | Other | 1: Intraoral Squamous Cell Carcinomas, 2: Cutaneous Malignant Tumors, 3: Breast Cancers, 4: Other tumors |
Primary outcome
Measurement of oxygen levels in tissues in response to hyperoxic therapy
Time frame: From time of ink injection to the time the ink is removed through surgical resection. This can range from days to years, or until the study's completion of enrollment, anticipated in 2020.
This study will assess whether the addition of hyperoxic therapy (100% oxygen delivered through a non-rebreather face mask) will increase the oxygen level of a tumor or tumor bed by > 5 mm Hg using EPR oximetry. Tumor oxygen values will be reported in millimeters of mercury (mmHg).
4 secondary outcomes
Characterize oxygen changes in tumor beds throughout the course of radiation therapy
Time frame: From time of ink injection through the completion of radiation therapy; an average of 4 months.
Characterize oxygen changes in tumors throughout the course of radiation therapy
Time frame: From time of ink injection through the completion of radiation therapy; an average of 4 months.
Characterize oxygen changes in tumor and tumor beds prior to radiation therapy
Time frame: From time of ink injection through the completion of medical treatment for cancer; an average of 4 months.
Characterize oxygen changes in tumor and tumor beds through the course of radiation therapy
Time frame: From time of ink injection through the completion of medical treatment for cancer; an average of 6 months.
Results and safety
The study was stopped early (reason given: The research team is exploring device optimization). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2019.
- Background: PubMed 8259056Bacic G, Liu KJ, O'Hara JA, Harris RD, Szybinski K, Goda F, Swartz HM. Oxygen tension in a murine tumor: a combined EPR and MRI study. Magn Reson Med. 1993 Nov;30(5):568-72. doi: 10.1002/mrm.1910300507.
- Background: PubMed 12465107Baudelet C, Gallez B. How does blood oxygen level-dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors? Magn Reson Med. 2002 Dec;48(6):980-6. doi: 10.1002/mrm.10318.
- Background: PubMed 8968082Brizel DM, Scully SP, Harrelson JM, Layfield LJ, Dodge RK, Charles HC, Samulski TV, Prosnitz LR, Dewhirst MW. Radiation therapy and hyperthermia improve the oxygenation of human soft tissue sarcomas. Cancer Res. 1996 Dec 1;56(23):5347-50.
- Background: PubMed 9226314Brizel DM, Sibley GS, Prosnitz LR, Scher RL, Dewhirst MW. Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int J Radiat Oncol Biol Phys. 1997 May 1;38(2):285-9. doi: 10.1016/s0360-3016(97)00101-6.
- Background: PubMed 15366029Charlier N, Beghein N, Gallez B. Development and evaluation of biocompatible inks for the local measurement of oxygen using in vivo EPR. NMR Biomed. 2004 Aug;17(5):303-10. doi: 10.1002/nbm.902.
- Background: PubMed 1735678Chaplin DJ, Horsman MR. Tumor blood flow changes induced by chemical modifiers of radiation response. Int J Radiat Oncol Biol Phys. 1992;22(3):459-62. doi: 10.1016/0360-3016(92)90853-a.
- Background: PubMed 8084241Dardzinski BJ, Sotak CH. Rapid tissue oxygen tension mapping using 19F inversion-recovery echo-planar imaging of perfluoro-15-crown-5-ether. Magn Reson Med. 1994 Jul;32(1):88-97. doi: 10.1002/mrm.1910320112.
- BackgroundDemidenko E. Mixed models: theory and applications with R. John Wiley & Sons; 2013 Aug 26.
- Background: PubMed 15667971Dewhirst MW, Poulson JM, Yu D, Sanders L, Lora-Michiels M, Vujaskovic Z, Jones EL, Samulski TV, Powers BE, Brizel DM, Prosnitz LR, Charles HC. Relation between pO2, 31P magnetic resonance spectroscopy parameters and treatment outcome in patients with high-grade soft tissue sarcomas treated with thermoradiotherapy. Int J Radiat Oncol Biol Phys. 2005 Feb 1;61(2):480-91. doi: 10.1016/j.ijrobp.2004.06.211.
- Background: PubMed 8524017Dunn JF, Ding S, O'Hara JA, Liu KJ, Rhodes E, Weaver JB, Swartz HM. The apparent diffusion constant measured by MRI correlates with pO2 in a RIF-1 tumor. Magn Reson Med. 1995 Oct;34(4):515-9. doi: 10.1002/mrm.1910340405.
- Background: PubMed 27526132Flood AB, Satinsky VA, Swartz HM. Comparing the Effectiveness of Methods to Measure Oxygen in Tissues for Prognosis and Treatment of Cancer. Adv Exp Med Biol. 2016;923:113-120. doi: 10.1007/978-3-319-38810-6_15.
- Background: PubMed 15366026Gallez B, Baudelet C, Jordan BF. Assessment of tumor oxygenation by electron paramagnetic resonance: principles and applications. NMR Biomed. 2004 Aug;17(5):240-62. doi: 10.1002/nbm.900.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip E Schaner, M.D., Ph.D. principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neoplasms, Malignant and Breast Neoplasm, run by Philip Schaner at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 19 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: The research team is exploring device optimization). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of oxygen levels in tissues in response to hyperoxic therapy (time frame: From time of ink injection to the time the ink is removed through surgical resection. This can range from days to years, or until the study's completion of enrollment, anticipated in 2020.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03321903, which also lists 71 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2019.