Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Healthy women presenting to enrollment sites for routine annual mammographic examinations, confirmed to have BI-RADS category c or d breast composition (density).

Routine screening mammography exam, CC + MLO views.

Routine Full-Field Digital Mammography

Routine screening tomosynthesis exam, CC + MLO views.

Routine Digital Breast Tomosynthesis

Bilateral breast ultrasound performed as an adjunct to mammography.

Automated Whole Breast Ultrasound

Mary W Yamashita, MD

The SoftVue™ is a whole breast ultrasound system with an automated scanning curvilinear ring-array transducer that employs UST. It is currently cleared under FDA 510(k) K123209 and K142517 for use as both a B-mode ultrasonic breast imaging system and color imaging of transmission data (sound speed and attenuation). SoftVue™ is not intended to be used as a replacement for screening mammography.

SoftVue uses non-ionizing ultrasound energy to generate tomographic image volumes of the whole breast. While the patient lays prone on a padded table with one breast comfortably submerged in a bath of warm water, a ring-shaped transducer, 22 cm in diameter, encircles the breast and pulses low-frequency sound waves through the water and into the breast tissue. More than 2000 elements in the curvilinear transducer's 360 degree array emit and receive ultrasound signals to analyze echoes from the breast anatomy in all directions, from the chest wall to the nipple. Not only does SoftVue capture data from the reflection of the sound waves off of tissue boundaries and structures within the breast, but because the transducer surrounds the whole breast, SoftVue also captures signals that are transmitted through the breast. This additional transmission data enhances the visualization of the anatomic structure of the breast tissue and is not currently available in any other commercially marketed breast ultrasound device.

This prospective, multicenter, multi-arm, clinical case collection program is IRB-approved and will be conducted in compliance with Good Clinical Practice, the Declaration of Helsinki and all applicable regulatory requirements. Arm 1 aims to collectively enroll up to 17,500 women at a total of up to 8 clinical sites. The design of this protocol is strictly limited to case collection; all investigational and statistical plans for future analyses will be prepared and registered separately, if they are applicable to the requirements of FDAAA 801.

Arm 1 is limited to the cohort of asymptomatic women, with heterogeneously or extremely dense breast parenchyma (BI-RADS breast composition category c or d). Matched triads of 2D digital mammography (FFDM), 3D digital mammography (DBT), and SoftVue automated whole breast ultrasound (SV)exams, from the same patient, with demographic information and clinical outcome data, will be collected during the same screening imaging episode. Ultrasound characteristics for all types of lesions, whether they are benign or malignant, will be collected, as well as objective and subjective breast density composition data.

The exams and clinical data accumulated in this prospective case collection (PCC) protocol will populate a database from which future investigations may be designed for peer reviewed publication, development of user training curriculums, building teaching case, and creating new marketing materials for SoftVue.A subset of exams will be sampled from Arm 1 for use in ROC Reader Study (protocol DMT-2015.002), which will be separately registered and is designed to evaluate the safety and efficacy of a new screening indication for use of SoftVue™ as an adjunct to screening mammography. The results of this ROC Reader Study will be submitted to the FDA for their consideration of a PMA application for SoftVue.

MEDICAL DEVICES:

* SoftVue™ (SV) automated whole breast ultrasound system, 510(k) Cleared for B-Mode ultrasound breast imaging, manufactured by Delphinus Medical Technologies.
* SoftVue™ with device modifications (software, hardware, user-interface), safety-tested for human use to complete feasibility, verification, and validation testing as a routine part of product development and performed in accordance with FDA 21 CFR 812.2 (b), manufactured by Delphinus Medical Technologies.
* Full-field digital mammography (FFDM), FDA Approved for breast screening and diagnosis, various manufacturers.
* Digital breast tomosynthesis (DBT), FDA Approved for breast screening and diagnosis, various manufacturers.

OBJECTIVES:

* Primary: To establish a library of cases for use in future SoftVue™ research studies, user training, and marketing.
* Secondary: Determine the frequency and severity of adverse events (AEs) to further evaluate the safety of SoftVue.

ENDPOINTS:

From multiple clinical sites whichever comes first:

* Up to 17,500 total enrolled subjects
* Up to 105 total breast cancer cases detected at program entry screening
* At least 35 total discordant breast cancer cases, where FFDM is negative or benign (BI-RADS 1 or 2) but SV is incomplete (BIRADS 0) and diagnostic imaging workup of SV findings leads to breast biopsy with malignant pathology

SITES:

At least six (≥ 6) qualified clinical sites in the United States

* MQSA Certified
* Digital Breast Tomosynthesis Screening Program Implemented
* Academic, Community Hospital, or Private Practice Setting

PROJECT DESIGN AND PROCEDURES:

* Potential participants will be recruited from the group of women presenting for their annual breast imaging exams at multiple clinical sites utilizing 3D DBT and 2D FFDM (non-synthesized) for routine screening.
* Asymptomatic women with heterogeneously or extremely dense breast parenchyma (BI-RADS composition c or d), based on visual assessment of FFDM by trained site personnel, will be invited to consider volunteering to participate in the case collection program.
* All participants will complete the same routine screening FFDM + DBT evaluation for which they originally reported to the clinic, with a complete set of 2D views and 3D views.
* Eligible patients will receive SV as an adjunct to FFDM + DBT.
* A single Investigator (radiologist) at each site will perform sequential review of the same subjects FFDM, DBT, and SV images.
* FFDM will be evaluated for final parenchymal density (BI-RADS a through d) and then each exam will be assigned to one of 3 BI-RADS assessment categories (0, 1, 2) by the radiologist.
* Abnormal findings will be indicated by a BI-RADS assessment category of 0 (Incomplete)and will undergo diagnostic imaging evaluations consistent with universally accepted standards of care.
* All evaluation results, diagnosis and treatment outcomes will be recorded.
* Normal findings will be indicated by BI-RADS assessment categories of 1 or 2 (Negative or Benign) which will be associated with a management recommendation to resume routine screening in one year, unless symptoms or signs of breast cancer develop in the interim.
* All participants who are not diagnosed with breast cancer as a direct result of the program entry examinations, incidental evaluations, or interval symptoms, will return to the site in 12 months for their next annual screening exam, the results and outcome of which will be recorded.
* Cancer status for all participants will be surveyed from program entry until and including the completion of recommended follow-up.
* A case will be determined cancer negative if the participant has no findings suspicious for cancer throughout the interval between program entry and completion of annual follow-up.
* A case will be determined cancer positive if a pathological evaluation confirms a breast cancer diagnosis during the interval between program entry and completion of annual follow-up.

STATISTICAL ANALYSIS:

* Demographic characteristics (age, race, and ethnicity) and other baseline characteristics (e.g., project arm, project site, breast density, lesion-specific characteristics) will be tabulated for all participants.
* A flow diagram or table will illustrate patient disposition ("accountability of patient cohort") including reasons for ineligibility and/or unevaluability.
* Safety will be summarized for all enrolled women. With the exception of anticipated events, adverse events (AEs) and serious adverse events (SAEs), occurring from the time of enrollment (SoftVue) and for 24 hours following the conclusion of the SoftVue exam, will be recorded.
* A separate statistical plan will be developed for any future analysis that includes justification of sample size and, if applicable to the requirements of FDAAA 801, will be registered separately in order to share the results.

Delphinus SoftVue Prospective Case Collection - ARM 1

ARM 1: A Prospective, Multicenter, Multi-arm, Clinical Case Collection Program to Acquire Breast Image Data and Establish an Image Library of Exams for Use in Future Research Studies, Training, and Product Development Efforts.

Non-Cancer cases, confirmed by normal or negative mammographic breast imaging (FFDM or DBT), or breast biopsy with benign pathology, after at least 365 days of follow-up

Cancer cases, confirmed by breast biopsy with malignant pathology, within 365 days of follow-up

Delphinus Medical Technologies, Inc.

Non-Interventional: Women presenting to enrollment sites for diagnostic examinations of symptoms or imaging findings, as recommended by a physician, and assigned BI-RADS category 4 or 5 (biopsy indicated).

Only standard care procedures will be performed for clinical intervention and diagnostic purposes.

Non-Interventional

Bilateral breast ultrasound images will be captured, but not clinically evaluated for diagnostic purposes by a physician.

The SoftVue™ is a whole breast ultrasound system with an automated scanning curvilinear ring-array transducer that employs UST. It is currently cleared under FDA 510(k) K123209 and K142517 for use as both a B-mode ultrasonic breast imaging system and color imaging of transmission data (sound speed and attenuation). SoftVue™ is not intended to be used as a replacement for screening mammography.

SoftVue uses non-ionizing ultrasound energy to generate tomographic image volumes of the whole breast. While the patient lays prone on a padded table with one breast comfortably submerged in a bath of warm water, a ring-shaped transducer, 22 cm in diameter, encircles the breast and pulses low-frequency sound waves through the water and into the breast tissue. More than 2000 elements in the curvilinear transducer's 360 degree array emit and receive ultrasound signals to analyze echoes from the breast anatomy in all directions, from the chest wall to the nipple. Not only does SoftVue capture data from the reflection of the sound waves off of tissue boundaries and structures within the breast, but because the transducer surrounds the whole breast, SoftVue also captures signals that are transmitted through the breast. This additional transmission data enhances the visualization of the anatomic structure of the breast tissue and is not currently available in any other commercially marketed breast ultrasound device.

This prospective, multicenter, multi-arm, clinical case collection program is IRB-approved and will be conducted in compliance with Good Clinical Practice, the Declaration of Helsinki and all applicable regulatory requirements. Arm 2 aims to collectively enroll up to 1,000 women at a total of up to 8 clinical sites. The design of Arm 2 in this protocol is strictly limited to case collection and is non-interventional; any investigational and/or statistical plans for future analyses will be prepared and registered separately, if they are applicable to the requirements of FDAAA 801.

Arm 2 is limited to the cohort of diagnostic female patients of any breast density composition category, who have been recommended for a breast biopsy (BI-RADS 4 or 5) after diagnostic imaging, or who have confirmed imaging findings. Matched sets of diagnostic imaging and SV exams, from the same patient, demographic information, and clinical outcome data, will be collected during diagnostic workup. Ultrasound characteristics for all types of lesions, whether they are benign or malignant, will be collected as well as objective and subjective breast density composition data. Ultrasound image data may be acquired with modified SoftVue devices, which have passed safety and quality evaluations per Delphinus' quality management system (QMS) and satisfy design change control standards, at select clinical sites in accordance with 21 CFR 812.2 (b), as a routine part of feasibility, validation, and verification testing for engineering and product development purposes.

The exams and clinical data accumulated in this prospective case collection (PCC) protocol will populate a database from which future investigations may be designed for peer reviewed publication, development of user training curricula, building teaching case, and creating new marketing materials for SoftVue.

MEDICAL DEVICES:

* SoftVue™ (SV) automated whole breast ultrasound system, 510(k) Cleared for B-Mode ultrasound breast imaging, manufactured by Delphinus Medical Technologies.
* SoftVue™ with device modifications (software, hardware, user-interface), safety-tested for human use to complete feasibility, verification, and validation testing as a routine part of product development and performed in accordance with FDA 21 CFR 812.2 (b), manufactured by Delphinus Medical Technologies.
* Full-field digital mammography (FFDM), FDA Approved for breast screening and diagnosis, various manufacturers. (If clinically indicated)
* Digital breast tomosynthesis (DBT), FDA Approved for breast screening and diagnosis, various manufacturers.
* Handheld Ultrasound (HHUS), FDA-Cleared for diagnostic breast imaging, various manufacturers. (If clinically indicated)
* Other diagnostic tests and medical device examinations of the breast, including, but not limited to MRI, BSGI, PET, biopsy, and elastography, on the order of a licensed physician, when clinically indicated.

OBJECTIVES:

* Primary: To establish a library of cases for use in future SoftVue™ research studies, user training, and marketing.
* Secondary: Determine the frequency and severity of adverse events (AEs) to further evaluate the safety of SoftVue.

ENDPOINTS:

From multiple clinical sites whichever comes first:

• Up to 1,000 total enrolled subjects

SITES:

At least six (≥ 6) qualified clinical sites in the United States

* MQSA Certified
* Digital Breast Tomosynthesis Screening Program Implemented
* Academic, Community Hospital, or Private Practice Setting

PROJECT DESIGN AND PROCEDURES:

* Potential participants will be recruited from the group of women presenting for diagnostic evaluation or biopsy at multiple clinical sites.
* All participants will complete the same standard care diagnostic evaluations that were recommended by a physician
* Eligible patients will receive a SV scan at the time of their scheduled diagnostic appointments, preferably prior to biopsy
* Investigators at the sites will compare SV images to the accompanying diagnostic images and pathology results
* No clinical SV interpretation will be performed and no clinical interventions will be made or changed based on SV images
* All evaluation results, diagnosis and treatment outcomes will be recorded
* Cancer status for all participants will be surveyed from program entry until and including the completion of physician recommended diagnostic workup
* A case will be determined cancer negative if the participant has non-malignant breast biopsy findings or confirmed non-suspicious diagnostic breast imaging findings
* A case will be determined cancer positive if a pathological evaluation confirms a breast cancer diagnosis (malignancy)

STATISTICAL ANALYSIS:

* Demographic characteristics (age, race, and ethnicity) and other baseline characteristics (e.g., project arm, project site, breast density, lesion-specific characteristics) will be tabulated for all participants.
* A flow diagram or table will illustrate patient disposition ("accountability of patient cohort") including reasons for ineligibility and/or unevaluability.
* Safety will be summarized for all enrolled women. With the exception of anticipated events, adverse events (AEs) and serious adverse events (SAEs), occurring from the time of enrollment (SoftVue) and for 24 hours following the conclusion of the SoftVue exam, will be recorded.
* A separate statistical plan will be developed for any future analysis that includes justification of sample size and, if applicable to the requirements of FDAAA 801, will be registered separately in order to share the results.

Delphinus SoftVue Prospective Case Collection - ARM 2

ARM 2: A Prospective, Multicenter, Multi-arm, Clinical Case Collection Program to Acquire Breast Image Data and Establish an Image Library of Exams for Use in Future Research Studies, Training, and Product Development Efforts.

Non-Cancer cases, confirmed by normal or negative breast imaging findings or concordant breast biopsy with benign pathology.

Cancer cases, confirmed by breast biopsy with malignant pathology

Mammary Neoplasms, Animal

Two dose levels will be evaluated in Arm A (without lymphodepletion)

Two dose levels will be evaluated in Arm B (with lymphodepletion)

Arm A -- Two dose levels will be evaluated:

Dose level One: 1.00E+06

Dose level Two: 1.00E+07

HTR2 T Cells

Arm B -- Two dose levels will be evaluated:

Dose level Two: 1.00E+07

Dose Level Three: 1.00E+08

Valentina Hoyos, MD

Wendy Callejas

Wendy Callejas, MD

The purpose of this study is to find the biggest dose of HTR2 T cells that is safe, to see how long these cells last in the body, to learn the side effects, and to see if these cells are able to fight and kill HER2 expressing breast cancer.

Patients eligible for this study have metastatic breast cancer that has HER2 expression and has progressed on at least one line of therapy. This is a gene transfer research study using special immune cells called T cells. T cells are a type of white blood cell that helps the body recognize and fight cancer cells.

The body has different ways of fighting diseases and no single way seems perfect for fighting cancer. This research combines two different ways of fighting cancer: antibodies and T cells. Antibodies are proteins that protect the body from infectious disease and possibly cancer. T cells, or T lymphocytes, are special blood cells that can kill other cells, including tumor cells. Both antibodies and T cells have shown promise treating cancer but have not been strong enough to cure most patients.

Previous research has found that investigators can put genes into T cells that helps them recognize cancer cells and kill them. Investigators now want to see if by putting a new gene in those T cells to help recognize breast cancer cells expressing HER2 can kill the cancer cells. In clinical trials for various cancer types that express HER2, our center engineered a CAR that recognizes HER2 and put this CAR into patients own T cells and gave them back. Investigators saw that the cells did grow and patients did tolerate and respond to the treatment.

Investigators will add a gene to the HER2 recognizing CAR T cells that will improve the T cells function. Investigators know that some immune cells in the body can lower T cells ability to kill cancer cells. Investigators have identified an antibody that will inactivate those immune suppressive cells thereby allowing T cells to survive better to recognize and kill cancer cells. This antibody targets the Trail-R2 receptor and is referred to as TR2.

Also, investigators know that T cells need the support of cytokines to perform their immune functions. There is evidence showing that the addition of interleukin 15 (IL15) enhances CAR T cells ability to kill cancer cells. As a result, investigators also added IL15 to the HER2 and TR2 targeting CAR T cells (HTR2 T cells).

The HTR2 T cells are an investigational product not approved by the Food and Drug Administration.

To make the T cells, the investigators will take the patient's blood and stimulate it with growth factors to make T cells grow. Investigators use a retrovirus to insert HER CAR, TR2 antibody and IL 15 genes into the T cells.

HTR2 cells are generated from the patient's T cells and are frozen. At the time the patient is scheduled to be treated, the cells will then be thawed and injected into the patient over 5 to 10 minutes. Patients will only get one dose of HTR2 T cells during the infusion. If the patient has a good response and tolerance, we may be able to repeat infusion in the future. The patent may be pretreated with Tylenol and Benadryl to prevent possible allergic reaction to the T cell administration.

If investigators need to stop the HTR2 T cells due to bad side effects, investigators have inserted a gene called iCasp9 into the T cells. This allows investigators to eliminate the HTR2 T cells in the blood when the gene comes into contact with a medication called Rimiducid. The drug Rimiducid is not yet FDA approved and is an experimental drug, but it has been tested in humans without bad side-effects. Investigators will only use this drug to kill the T cells if necessary due to side effects. Since investigators do not know exactly what dose will effectively stop HTR2 T cells in individual patients, investigators will start at a low dose with the ability to increase the dose two more times based on how patients are doing. Blood work will be done to ensure that the HTR2 T cells have been successfully eliminated.

The treatment will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital.

MEDICAL TESTS BEFORE TREATMENT

Before being treated, patients will receive a series of standard medical tests:

* Physical exam and history
* Blood tests to measure blood cells and organ function
* Measurements of the tumor by scans at baseline prior to treatment
* Ultrasound of the heart to make sure the patient has good baseline cardiac function

Additionally, patients will need a biopsy of their tumor tissue to both confirm HER2 expression and to be used for research purposes.

MEDICAL TESTS DURING AND AFTER TREATMENT

Within four weeks after infusion, patients will be monitored on a weekly basis for dose limiting side effects of the HTR2 T cells:

* Physical exam and history
* Blood tests to measure blood cells and organ function

After the initial six weeks, patients will be monitored at a minimum every 3 months for the 1st year and every 6 months between 1 to year 5 or as frequently as deemed necessary:

* Physical exam and history
* Blood tests to measure blood cells and organ function
* Measurements of patient's tumor by scans to assess treatment response

To learn more about the way T cells work in the patient's body, investigators will obtain up to 50 ml of blood from patient before chemotherapy, before the T-cell infusion, 1 to 4 hours, 1, 2, 3, 4 weeks and 8 weeks after infusion, every 3 months for a year followed by every 6 months for 4 years and then every year for the the next 10 years. Total participation on this study will be 15 years. During the time points listed above, if the T cells are found in the blood at a certain amount, an extra half a tablespoon of blood may be needed for additional testing.

Investigators will obtain one tissue biopsy within 4 weeks after infusion and as clinically indicated thereafter. If additional clinically indicated tumor biopsies are obtained, investigators will ask for a portion of the sample for research.

TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer

(TRAILBLASER) TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor T Cells for the Treatment of Metastatic Breast Cancer

Rate of incidents of dose limiting toxicity by dose levels.

Proportion of subjects with best overall response of complete response (CR) or partial response (PR) according to RECIST criteria

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Delphinus SoftVue Prospective Case Collection - ARM 1	NCT03257839	Breast Neoplasm...	Routine Full-Fi... Routine Digital... Automated Whole...	18 Years -	Delphinus Medical Technologies, Inc.
Delphinus SoftVue Prospective Case Collection - ARM 2	NCT02977247	Breast Neoplasm...	Non-Interventio... Automated Whole...	18 Years -	Delphinus Medical Technologies, Inc.
TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer	NCT06251544	Breast Cancer Tumor, Breast Breast Tumor Malignant Neopl... Mammary Cancer Mammary Neoplas... Mammary Neoplas... Neoplasm, Breas...	HTR2 T Cells HTR2 T Cells	18 Years - 80 Years	Baylor College of Medicine
TRAIL-R2 and HER2 Bi-Specific Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Metastatic Breast Cancer	NCT06251544	Breast Cancer Tumor, Breast Breast Tumor Malignant Neopl... Mammary Cancer Mammary Neoplas... Mammary Neoplas... Neoplasm, Breas...	HTR2 T Cells HTR2 T Cells	18 Years - 80 Years	Baylor College of Medicine

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