Contrast Ultrasound Detection of Sentinel Lymph Nodes

NCT02652923 | Completed Phase 1 DMC

• 2 other identifiers: 15P.487R01CA172336
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two part, open label, non-randomized trial of women with a breast cancer diagnosis scheduled for excisional surgery and sentinel lymph node (SLN) evaluation. Part 1 is a two-period, crossover, dose-finding study, which will be performed in 12 healthy female volunteers to determine the optimal dose as well as the safety and tolerability of the tissue-specific, contrast agent Sonazoid (GE Healthcare, Oslo, Norway) for human lymphatic applications. In Part 2 lymphosonographic SLN identification will be compared to that of isotope mapping during surgery on 90 female, breast cancer patients.

Conditions

Breast Cancer

Keywords

ultrasound contrast agent; lymphosonography; breast cancer

Outcome Measures

Primary Outcomes (3)

• Dose optimization (1.0 vs 2.0 ml) based on the degree and duration of Sonazoid contrast-enhancement of the visualized LCs and SLNs

  To establish, in healthy, female volunteers, the optimal dose of subdermaly administrated Sonazoid (an ultrasound contrast agent) employed for contrast enhanced ultrasound imaging (CEUS)

  Up to 4 months

• Number of subdermal Sonazoid volunteers with AEs, clinical assessments, and safety laboratory tests outside normal ranges (established by historical controls)

  To assess the safety and tolerability of subdermal administration of Sonazoid in 12 female, healthy volunteers.

  Up to 4 months

• Number SLNs in patients with breast cancer identified by lymphosonography and by isotope mapping with Tc-99m sulfur colloids.

  To determine if CEUS of subdermally administrated Sonazoid (i.e., lymphosonography) identify more sentinel lymph nodes (SLNs) in patients with breast cancer compared to isotope mapping (with Tc-99m sulfur colloids) using blue dye and surgical dissection as the reference standard. The fundamental hypothesis is that on average lymphosonography will detect 3.2 SLNs compared to 2.7 with isotope mapping.

  Up to 34 months

Study Arms (2)

Part 1 - volunteers

EXPERIMENTAL

Subdermal low (1.0 ml) or high (2.0 ml) dose injection of the ultrasound contrast agent Sonazoid divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock) around a 2 cm in diameter region in the mid-upper outer quadrant of the left breast, followed a week later by the other dose injected in the same fashion into the right breast.

Drug: Sonazoid; Perflubutane for Injection

Part 2 - patients

EXPERIMENTAL

Subdermal injection of the ultrasound contrast agent of Sonazoid divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock) around the breast cancer. Subjects will receive an injection of either a low (1.0 ml) or a high (2.0 ml) dose of Sonazoid depending on the outcome of the Part 1 safety and tolerability study.

Drug: Sonazoid; Perflubutane for Injection

Interventions

Sonazoid; Perflubutane for Injection DRUG

subdermal injection into the breast of Sonazoid (1 or 2 ml) divided into four individual aliquots at four locations (12, 3, 6, and 9 o'clock)

Also known as: ultrasound microbubble contrast agent

Part 1 - volunteers; Part 2 - patients

Eligibility Criteria

• Age: 21 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Part 1:
• Be female.
• Be at least 21 years of age.
• Must have a body mass index (BMI) greater or equal to 19 and less than or equal to 33.
• Be able to comprehend the full nature, purpose and risks of the study.
• Part 2:
• Be female.
• Be diagnosed with breast cancer.
• Be scheduled for a surgical excision with SLN evaluation.
• Be at least 21 years of age.
• Be medically stable.
• If of child-bearing potential, must have a negative pregnancy test.
• Be able to comply with study procedures.
• Have read and signed the IRB-approved Informed Consent form for participating in the study.

You may not qualify if:

• Part 1:
• A history of chest wall trauma or surgery, or dermatologic disorders, which could be expected to disrupt lymphatic drainage of the chest wall.
• A history of surgical breast augmentation, reduction, or biopsy.
• Lymphedema or chronic edema.
• Females who are pregnant or nursing or are actively lactating.
• Exposure to ultrasound contrast agents in the 1 month prior to study initiation.
• Known hypersensitivity to ultrasound contrast agents.
• Patients with a history of anaphylactic allergy to eggs or egg products, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock.
• Significant axillary, supraclavicular, or other chest wall palpable adenopathy.
• Evidence of current ongoing illicit drug use or average alcohol use of greater than 2 drinks a day.
• Use of more than 5 cigarettes/day.
• Participation in an investigational drug study within the period starting 1 month before study drug administration.
• Subject is mentally or legally incapacitated, has significant emotional problems at the time of prestudy (screening) visit or expected during the conduct of the study or has a history of a clinically significant psychiatric disorder within the last 5 years. Subjects who have had situational depression may be enrolled in the study at the discretion of the Investigator.
• Subject has a history of any illness that, in the opinion of the study Investigator, might confound the results of the study or poses an additional risk to the subject by his participation in the study.
• An estimated creatinine clearance of ≤80 ml/min based on the Cockcroft-Gault equation. An actual creatinine clearance, as determined by a 24 hour urine collection, may be used in place of the Cockcroft-Gault equation. Subjects who have an actual or estimated creatinine clearance 70 ml/min may be enrolled at the discretion of the investigator.

Sponsors & Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University: lead
• National Cancer Institute (NCI): collaborator
• GE Healthcare: collaborator
• Siemens Medical Solutions: collaborator

Study Sites (1)

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Sonazoid; perfluorobutane; Injections

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Flemming Forsberg, PhD

  Radiology; Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 12, 2016
• Study Start: January 1, 2016
• Primary Completion: January 12, 2022
• Study Completion: January 12, 2022
• Last Updated: January 23, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)