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

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will test the use of focused ultrasound ablation, low-dose gemcitabine (a chemotherapy) and the combination of focused ultrasound ablation plus low-dose gemcitabine in patients with early-stage breast cancers. We will be testing the effects of each of these regimens on cells in the immune system. We hypothesize that the combination of focused ultrasound ablation and gemcitabine will decrease myeloid-derived suppressor cells and will increase T cell activity. We also hypothesize that focused ultrasound ablation and low-dose gemcitabine will be safe and will result in non-inferior surgical completion rates and tumor margin assessments.

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.

What data supports the effectiveness of the treatment Focused Ultrasound + Gemcitabine for Breast Cancer?

Research shows that combining focused ultrasound with gemcitabine has been effective in treating pancreatic cancer, suggesting potential benefits for other cancers like breast cancer. ^{1 2 3 4 5}

Is the combination of focused ultrasound and gemcitabine safe for humans?

Studies have shown that the combination of focused ultrasound and gemcitabine is generally safe in humans, particularly in treating pancreatic cancer, with some patients experiencing manageable side effects like myelosuppression (a decrease in blood cell production). ^{1 2 3 4 6}

How is the treatment of focused ultrasound combined with gemcitabine unique for breast cancer?

This treatment is unique because it combines focused ultrasound, a non-invasive method that uses sound waves to target tumors, with gemcitabine, a chemotherapy drug, potentially enhancing the drug's effectiveness and reducing side effects compared to traditional chemotherapy alone. ^{1 2 3 7 8}

Research Team

Patrick Dillon, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Group II: Arm B: FUS Experimental Treatment 1 Intervention

Group III: Arm A: GEM 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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Combination of chemotherapy and focused ultrasound for the treatment of unresectable pancreatic cancer: a proof-of-concept study. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

High-intensity focused ultrasound therapy in combination with gemcitabine for unresectable pancreatic carcinoma. [2020]

3. China pubmed.ncbi.nlm.nih.gov

[Effect of high-intensity focused ultrasound combined with gemcitabine on subcutaneous pancreatic cancer in nude mice]. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

HIFU is safe, effective, and feasible in pancreatic cancer patients: a monocentric retrospective study among 523 patients. [2022]

5. China 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]. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Gemcitabine and UFT plus oral calcium folinate: phase I study. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Chronic effects of pulsed high intensity focused ultrasound aided delivery of gemcitabine in a mouse model of pancreatic cancer. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Combination of Focused Ultrasound, Immunotherapy, and Chemotherapy: New Perspectives in Breast Cancer Therapy. [2023]