Focused Ultrasound + Gemcitabine for Breast Cancer

(Breast 54 Trial)

Overseen By Olena Glushakova, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Patrick Dillon, MD

Must not be taking: Systemic steroids

Disqualifiers: Pregnancy, Immunodeficiency, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 3 weeks

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new methods to treat early-stage breast cancer using focused ultrasound, which targets tumors with sound waves, and a low dose of the chemotherapy drug gemcitabine. The goal is to determine how these treatments, alone or combined, affect the immune system and assess their safety. The trial seeks participants with newly diagnosed breast cancer or a localized recurrence, who have high-risk features such as large tumors or lymph node involvement. Participants must have a tumor accessible by focused ultrasound. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic steroid therapy, you may need to adjust your dosage or stop, unless it's for adrenal or pituitary insufficiency. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that focused ultrasound safely and effectively treats breast cancer. This method uses sound waves to target cancer cells and has received positive feedback from patients in past studies.

Gemcitabine, a chemotherapy drug approved for breast cancer treatment, is safely used alongside other therapies. Large studies have found that patients generally tolerate it well, with manageable side effects.

In summary, previous research has demonstrated the safety of both focused ultrasound and gemcitabine. While minor side effects can occur, they are usually manageable. Overall, both treatments are considered safe for breast cancer patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel approach to tackling breast cancer. Unlike traditional chemotherapy, which uses drugs to kill cancer cells, focused ultrasound (FUS) uses sound waves to target and potentially destroy tumor tissue with precision. This technique could minimize damage to surrounding healthy tissue and reduce side effects. Additionally, when combined with Gemcitabine, a chemotherapy drug, FUS might enhance the drug's effectiveness by improving its delivery to the cancer cells. This combination could lead to more effective treatment outcomes with potentially less toxicity compared to standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that focused ultrasound, one of the treatments in this trial, can effectively target and destroy tumor cells in breast cancer. In various studies, focused ultrasound has completely destroyed tumors in 20% to 100% of cases, highlighting its potential as a strong treatment option. Meanwhile, gemcitabine, another treatment in this trial, has shown promising results in treating breast cancer. Specifically, it has improved survival in patients with advanced breast cancer and offers benefits similar to other chemotherapy treatments. This trial will evaluate the combination of focused ultrasound with gemcitabine, which might enhance the immune system's ability to fight cancer cells, making it a promising approach for treating early-stage breast cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Patrick Dillon, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed breast cancer stages 1-3, regardless of hormone receptor status. Participants must have a lesion accessible to focused ultrasound and be willing to provide tissue samples. They should have good performance status (ECOG 0-2) and adequate organ function. Exclusions include those with breast implants on the treatment side, prior treatments for current cancer, pregnancy, certain steroid therapies or immunodeficiencies, known allergies to gemcitabine, other active cancers or infections.

Inclusion Criteria

Willing and able to provide written consent

Stated willingness to comply with all study procedures and availability for the duration of the study

I am willing to undergo a biopsy to provide a tissue sample.

Exclusion Criteria

I haven't taken high doses of steroids or have an immune system problem recently.

You have a medical or mental health condition that prevents you from taking part in the study.

Participants in whom there is a medical contraindication or potential problem in complying with the requirements of the protocol in the opinion of the investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive focused ultrasound ablation, low-dose gemcitabine, or a combination of both

3 weeks

Multiple visits for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and surgical outcomes

7 months

Follow-up visits at month 7 and 30 days post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Focused Ultrasound
• Gemcitabine

Trial Overview The study examines the safety and immune system effects of three regimens: focused ultrasound ablation alone, low-dose gemcitabine chemotherapy alone, and their combination in early-stage breast cancer patients. It aims to see if these treatments can reduce suppressor cells that hinder immunity while boosting T cell activity without compromising surgery outcomes.

How Is the Trial Designed?

Group I: Arm C: GEM/FUS Experimental Treatment 1 Intervention

Group II: Arm B: FUS Experimental Treatment 1 Intervention

Focused Ultrasound is already approved in United States, European Union for the following indications:

Approved in United States as Gemzar for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Approved in European Union as Gemzar for:

• Metastatic breast cancer
• Non-small cell lung cancer
• Ovarian cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Patrick Dillon, MD

Lead Sponsor

Trials

2

Recruited

60+

Published Research Related to This Trial

In a study of 45 patients with unresectable pancreatic carcinoma, those receiving high-intensity focused ultrasound (HIFU) combined with gemcitabine had a significantly longer median survival time (8.91 months) and higher 6-month survival rate (73.9%) compared to those receiving gemcitabine alone (5.53 months and 40.9%, respectively).

The combination therapy also resulted in a higher clinical benefit rate (69.6% vs 36.3%) and a greater pain remission rate (65.2% vs 31.8%), suggesting that HIFU with gemcitabine may be a more effective treatment option for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound therapy in combination with gemcitabine for unresectable pancreatic carcinoma. Lv, W., Yan, T., Wang, G., et al.[2020]

Gemcitabine, a nucleoside analog, inhibits DNA synthesis and shows potential synergy with other antimetabolites like 5-fluorouracil, making it a promising treatment for solid tumors.

In a phase I study involving eight patients, the main side effect observed was myelosuppression, and the study aims to establish the maximum tolerated doses of gemcitabine when combined with UFT and oral calcium folinate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and UFT plus oral calcium folinate: phase I study. Philip, PA., Ibrahim, D., Zalupski, M., et al.[2022]

High-intensity focused ultrasound (HIFU) significantly reduces tumor growth in nude mice with human pancreatic cancer, showing a clear therapeutic effect compared to a control group.

Combining HIFU with the chemotherapy drug gemcitabine leads to the greatest reduction in tumor volume and the lowest expression of vascular endothelial growth factor (VEGF), suggesting that this combination is the most effective treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of high-intensity focused ultrasound combined with gemcitabine on subcutaneous pancreatic cancer in nude mice]. Mao, Y., Fang, L., Liu, L., et al.[2022]

In a study of 523 patients with unresectable pancreatic ductal adenocarcinoma, those treated with high-intensity focused ultrasound (HIFU) combined with gemcitabine (GEM) had a median overall survival of 7.4 months, compared to 6.0 months for those receiving GEM alone, indicating a significant survival benefit (P=0.002).

The combination therapy showed the greatest survival advantage in patients receiving HIFU along with regional intra-arterial chemotherapy (RIAC) and systemic chemotherapy, and importantly, there were no severe complications reported from the HIFU treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIFU is safe, effective, and feasible in pancreatic cancer patients: a monocentric retrospective study among 523 patients. Ning, Z., Xie, J., Chen, Q., et al.[2022]

The combination of focused ultrasound (FUS) and chemotherapy (nab-paclitaxel plus gemcitabine) was found to be safe, with no adverse effects or dose-limiting toxicities reported in a study involving nine patients with unresectable pancreatic cancer.

Patients in the intermediate-intensity FUS group experienced significant tumor size reductions (over 30%), decreased CA 19-9 levels, and improved survival rates, indicating promising preliminary efficacy for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study. Lee, JY., Oh, DY., Lee, KH., et al.[2023]

The combination of pulsed high intensity focused ultrasound (pHIFU) and gemcitabine (gem) was well tolerated in a mouse model of pancreatic tumors, showing effective tumor permeabilization and cell death in treated areas over a 2-5 week observation period.

pHIFU treatment significantly downregulated 162 genes associated with immunosuppression and chemoresistance, suggesting that this method not only enhances drug delivery but may also improve the immune response against tumors compared to gemcitabine treatment alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic effects of pulsed high intensity focused ultrasound aided delivery of gemcitabine in a mouse model of pancreatic cancer. Khokhlova, TD., Wang, YN., Son, H., et al.[2023]

Focused ultrasound is gaining traction as a promising treatment for breast cancer, which is the most common cancer in women, highlighting the need for more effective and personalized therapies with fewer side effects.

This review discusses the potential of combining therapeutic ultrasound with immunotherapy and chemotherapy, suggesting innovative approaches to enhance treatment outcomes for breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Focused Ultrasound, Immunotherapy, and Chemotherapy: New Perspectives in Breast Cancer Therapy. Dahan, M., Cortet, M., Lafon, C., et al.[2023]

In a study of 48 patients with intermediate and advanced pancreatic cancer, combining high intensity focused ultrasound (HIFU) with gemcitabine treatment led to significantly better outcomes compared to HIFU alone, including higher response rates and improved pain relief.

Patients receiving the combination treatment also experienced longer median survival times and better quality of life, indicating that this approach may enhance the overall therapeutic efficacy for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy evaluation of high intensity focused ultrasound combined with intra-arterial infusion of gemcitabine in the treatment of pancreatic cancer]. Zhong, GC., Zhang, XY., Chen, J., et al.[2022]

Citations

1. fusfoundation.org fusfoundation.org/posts/breast-cancer-clinical-trial-update-focused-ultrasound-plus-microbubbles-improves-the-effects-of-radiation-therapy/

Breast Cancer Clinical Trial Update The final results from the 20-patient study were published in May 2024 in PLoS Medicine. After 3 months, half (n=9) of the 18 tumors showed a ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2441491/

Image-guided focused ultrasound ablation of breast cancer Results of studies on FUS breast cancer ablation to date have been variable, with histopathologic analysis demonstrating complete tumour necrosis in 20% to 100% ...

3. fusfoundation.org fusfoundation.org/posts/focused-ultrasound-for-breast-fibroadenomas-five-year-durability-data/

Focused Ultrasound for Breast Fibroadenomas: Five-Year ... A single HIFU treatment substantially reduced the size and symptoms of breast fibroadenomas, and the effects lasted more than five years.

4. journals.plos.org journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004408

Radiation enhancement using focussed ultrasound-stimulated ... This study opens new avenues for improving treatment outcomes in breast cancer and the possibility of replication in other primary malignancies.

5. medrxiv.org medrxiv.org/content/10.1101/2024.09.10.24313423v1.full

High-intensity focused ultrasound in treatment of primary ... High-intensity focused ultrasound (HIFU), a known thermal ablative technique, has shown promising results in breast cancer treatment. Therefore, ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02794558

Study Details | NCT02794558 | Safety and Effectiveness of ... Study specific aim is to Coagulate the tissue volume of a proven breast cancer with MRgFUS and Collect post treatment follow-up clinical and radiological data ...

7. fusfoundation.org fusfoundation.org/posts/focused-ultrasound-for-breast-cancer-a-new-safe-promising-combination-treatment/

Focused Ultrasound for Breast Cancer: A Promising ... The research team concluded that combining focused ultrasound, microbubbles, and radiation therapy was safe and a promising treatment for breast cancer.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8608284/

High-Intensity Focused Ultrasound: A Review of Mechanisms ... High Intensity Focused Ultrasound (HIFU) is an emerging and increasingly useful modality in the treatment of cancer and other diseases.