Clinical trial NCT03321903: EPR Tumor Oximetry With CE India Ink
Official title: Tumor Oximetry Using Electron Paramagnetic Resonance (EPR) With India Ink (Using Carbon Particulates From Carlo Erba [CE])
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Neoplasms, Malignant
Breast Neoplasm
Carcinoma, Basal Cell
Carcinoma, Squamous Cell
Melanoma
Skin Neoplasm
Head and Neck Neoplasms
Keywords: Oxygen
Oximetry
Electron Spin Resonance Spectroscopy
Carbon
Charcoal
Radiotherapy
India Ink
EPR
ESR
Immunotherapy
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2017-10-26
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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.

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

1. Subject must be capable of giving informed consent or has an acceptable surrogate capable of giving consent on behalf of the subject.
2. 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.

   1. 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.

Exclusion Criteria:

1. Previous adverse reaction to a charcoal product e.g., a local hypersensitive response from a black tattoo or from ingestion of activated charcoal
2. Previous adverse reaction to the suspending agent
3. Subject has a pacemaker that is not known to be MRI compatible
4. Subject has a non-removable implant or device with metal that is not known to be MRI compatible
5. 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.

Primary outcomes:
measure: Measurement of oxygen levels in tissues in response to hyperoxic therapy
timeFrame: 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:
measure: Characterize oxygen changes in tumor beds throughout the course of radiation therapy
timeFrame: From time of ink injection through the completion of radiation therapy; an average of 4 months.
measure: Characterize oxygen changes in tumors throughout the course of radiation therapy
timeFrame: From time of ink injection through the completion of radiation therapy; an average of 4 months.
measure: Characterize oxygen changes in tumor and tumor beds prior to radiation therapy
timeFrame: From time of ink injection through the completion of medical treatment for cancer; an average of 4 months.
measure: Characterize oxygen changes in tumor and tumor beds through the course of radiation therapy
timeFrame: From time of ink injection through the completion of medical treatment for cancer; an average of 6 months.
Other outcomes:
measure: Tissue Histology
timeFrame: Approximately 30 days post-surgical excision of the tumor
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Philip E Schaner, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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