EPR Tumor Oximetry With CE India Ink

Melanoma Clinical Trial

Official title:

Tumor Oximetry Using Electron Paramagnetic Resonance (EPR) With India Ink (Using Carbon Particulates From Carlo Erba [CE])

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03321903
• Other study ID #: 29880 D17008
• Secondary ID: P01CA190193
• Status: Terminated
• Start date: August 30, 2017
• Est. completion date: October 27, 2019

Study information

• Verified date: December 2019
• Source: Dartmouth-Hitchcock Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: October 27, 2019
• Est. primary completion date: October 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Breast Neoplasm
• Breast Neoplasms
• Carcinoma
• Carcinoma, Basal Cell
• Carcinoma, Squamous Cell
• Head and Neck Neoplasms
• Melanoma
• Neoplasms
• Neoplasms, Malignant
• Skin Neoplasm
• Skin Neoplasms

Intervention

Device:
• Carlo Erba Ink Injection
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.

Other:
• EPR 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.

Locations

Country	Name	City	State
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire

Sponsors (2)

Lead Sponsor	Collaborator
Philip Schaner	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

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* Note: There are 71 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tissue Histology	For those subjects whose tumor is resected along with the tissue containing the India ink carbon particles as a part of their usual care, the tissue at the site of the injection will be submitted for processing with standard pathology procedures. Tissue sections spanning the injection site(s) will be evaluated for the extent and mechanism of dispersion and for the presence of acute or chronic inflammation or other tissue reaction (scar, fibrosis, capsule formation, or other). The tissue will be assessed as to whether the reaction observed is as expected for ink injections.	Approximately 30 days post-surgical excision of the tumor
Primary	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).	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	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).	From time of ink injection through the completion of radiation therapy; an average of 4 months.
Secondary	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).	From time of ink injection through the completion of radiation therapy; an average of 4 months.
Secondary	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).	From time of ink injection through the completion of medical treatment for cancer; an average of 4 months.
Secondary	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).	From time of ink injection through the completion of medical treatment for cancer; an average of 6 months.