Sonoporation + Chemotherapy for Pancreatic Cancer

Recruiting at 1 trial location

Overseen By Flemming Forsberg, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Flemming Forsberg

Must be taking: Chemotherapy

Disqualifiers: COPD, Unstable cardiac, Renal impairment, others

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

Compensation: Varies

Number of Visits: 1

Duration: 12-14 weeks

120 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves standard chemotherapy, it's best to discuss your current medications with the study team to ensure there are no interactions.

What data supports the effectiveness of the treatment Sonoporation + Chemotherapy for Pancreatic Cancer?

Research shows that combining nanoparticle albumin-bound paclitaxel with gemcitabine significantly improves survival in patients with metastatic pancreatic cancer compared to gemcitabine alone. This combination has become a standard treatment option due to its effectiveness in improving overall and progression-free survival. ^{1 2 3 4 5}

Is the combination of sonoporation and chemotherapy safe for treating pancreatic cancer?

The combination of gemcitabine and nanoparticle albumin-bound paclitaxel, used in treating pancreatic cancer, is generally well tolerated, though it can cause side effects like sepsis (a severe infection) and neutropenia (low white blood cell count). These side effects are manageable with proper monitoring and dose adjustments. ^{2 3 6 7 8}

What makes the Sonoporation + Chemotherapy treatment for pancreatic cancer unique?

This treatment uses ultrasound to enhance the delivery of chemotherapy drugs directly to the tumor, potentially increasing effectiveness and reducing side effects compared to traditional methods. It combines gemcitabine, irinotecan, and nab-paclitaxel with ultrasound-targeted microbubble destruction, which helps the drugs penetrate the tumor more effectively. ^{9 10 11 12 13}

What is the purpose of this trial?

This phase I/II trial studies the effect of sonoporation in addition to standard of care chemotherapy in treating patients with pancreatic cancer. Sonoporation is a novel method that uses ultrasound and microbubbles to increase therapeutic effect by increasing uptake or enhance sensitization. Sonoporation together with chemotherapy may work better in treating patients with pancreatic cancer compared to chemotherapy alone.

Research Team

Flemming Forsberg, PhD

Principal Investigator

Thomas Jefferson University

Eligibility Criteria

Adults over 18 with a new diagnosis of inoperable pancreatic cancer, visible on ultrasound, who can undergo standard chemotherapy. They must not be pregnant or breastfeeding and agree to use contraception. Participants should be relatively mobile (ECOG status 0-2) and have adequate blood counts and liver function.

Inclusion Criteria

Your white blood cell count is not too high.

My cancer is an advanced or spread pancreatic cancer.

Your AST and ALT levels in your blood should not be more than three times the upper limit of normal.

Exclusion Criteria

I have advanced pancreatic cancer and severe liver issues.

I am currently on life support or in a critical care unit.

I have worsening chest pain due to heart artery blockage.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive standard of care chemotherapy with or without sonoporation. Chemotherapy includes gemcitabine and nab-paclitaxel or FOLFIRINOX, with sonazoid and CEUS for the experimental arm.

12-14 weeks

Multiple visits (in-person) for chemotherapy administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up every 3 months.

Up to 3 years

Quarterly visits (in-person)

Treatment Details

Interventions

• Gemcitabine Hydrochloride
• Irinotecan Hydrochloride
• Nab-paclitaxel
• Sonoporation

Trial Overview The trial is testing sonoporation—a technique using ultrasound and microbubbles—combined with standard chemotherapy drugs for pancreatic cancer treatment. The goal is to see if this combination is more effective than chemotherapy alone.

Participant Groups

Group I: Arm I (sonazoid, ultrasound, chemotherapy) Experimental Treatment 11 Interventions

Patients receive standard of care chemotherapy consisting of gemcitabine hydrochloride and nab-paclitaxel IV over 60 minutes on days 1, 8 and 15 OR FOLFIRINOX IV on days 1 and 2. Treatments repeat every 28 days for up to 3 cycles for gemcitabine and nab-paclitaxel, and every 14 days for up to 7 cycles for FOLFIRINOX in the absence of disease progression or unacceptable toxicity. Patients also receive sonazoid IV over 20 minutes and undergo CEUS. Patients undergo CT or PET/CT or MRI during screening and as clinically indicated on study.

Group II: Arm II (chemotherapy) Active Control 9 Interventions

Patients receive standard of care chemotherapy consisting of gemcitabine hydrochloride and nab-paclitaxel IV over 60 minutes on days 1, 8 and 15 OR FOLFIRINOX IV on days 1 and 2. Treatments repeat every 28 days for up to 3 cycles for gemcitabine and nab-paclitaxel, and every 14 days for up to 7 cycles for FOLFIRINOX in the absence of disease progression or unacceptable toxicity. Patients undergo CT or PET/CT or MRI during screening and as clinically indicated on study.

Gemcitabine Hydrochloride is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Gemzar for:

• Non-small cell lung cancer
• Pancreatic cancer
• Breast cancer
• Ovarian cancer

Approved in United States as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Approved in Canada as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Approved in Japan as Gemzar for:

• Pancreatic cancer
• Non-small cell lung cancer
• Breast cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Flemming Forsberg

Lead Sponsor

Trials

1

Recruited

120+

Thomas Jefferson University

Lead Sponsor

Trials

475

Recruited

189,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study involving 221 patients with metastatic pancreatic ductal adenocarcinoma and poor performance status, the combination of NAB-paclitaxel and gemcitabine was found to be well tolerated, with manageable side effects such as anemia and neutropenia.

Both dosing regimens of NAB-paclitaxel (100 mg/m2 and 125 mg/m2) showed similar efficacy, with comparable response rates and median progression-free survival, indicating that this treatment is effective for fragile patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. Macarulla, T., Pazo-Cid, R., Guillén-Ponce, C., et al.[2022]

Nab-paclitaxel plus gemcitabine (nab-P/Gem) is an effective first-line treatment for metastatic pancreatic cancer, with median overall survival rates ranging from 8.7 to 13.5 months across various studies involving a diverse patient population.

The combination of nab-P/Gem with additional agents is being actively researched, showing promise for improving outcomes in advanced pancreatic cancer, with median overall survival extending up to 17 months in some cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

nab-Paclitaxel for the treatment of pancreatic cancer. Kim, G.[2023]

Gemcitabine-loaded human serum albumin nanoparticles (Gem-HSA-NPs) were successfully developed and showed a favorable controlled release, with an encapsulation rate of approximately 83% and a particle size of about 150 nm.

In vivo studies demonstrated that Gem-HSA-NPs significantly inhibited tumor growth in pancreatic cancer while exhibiting lower toxicity compared to other treatment groups, indicating their potential as a safer and more effective delivery method for gemcitabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. Yu, X., Di, Y., Xie, C., et al.[2022]

The combination of nab-paclitaxel, gemcitabine, and capecitabine was found to be well tolerated in a phase I study with 15 patients, establishing a maximum-tolerated dose (MTD) but showing only modest antitumor activity in metastatic pancreatic cancer.

Despite the regimen being generally safe, with a low incidence of severe hematologic toxicities, only 14.3% of patients had a partial response, indicating that optimizing dose intensity may be crucial for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. Ko, AH., Truong, TG., Kantoff, E., et al.[2022]

In a study of 11 patients with metastatic or recurrent pancreatic cancer, the combination of nab-paclitaxel and gemcitabine showed promising efficacy, with a 6-month overall survival rate of 66.7% and a disease control rate of 90.9%.

The treatment was well tolerated, with no treatment-related deaths and manageable side effects, making nab-paclitaxel plus gemcitabine a potential standard treatment for this aggressive cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. Takeda, Y., Katsura, Y., Ohmura, Y., et al.[2022]

Irinotecan hydrochloride, approved in 1996 for second-line treatment of metastatic colorectal cancer, is generally well tolerated and can be safely administered on an outpatient basis, demonstrating clinically relevant activity against the disease.

Both irinotecan and gemcitabine, which will be discussed in a subsequent article, have manageable side effects that can be addressed with proper monitoring and dose adjustments, highlighting the importance of oncology nurses in patient education and symptom management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. Stucky-Marshall, L.[2019]

In a phase 3 trial involving 861 patients with metastatic pancreatic cancer, the combination of nab-paclitaxel and gemcitabine significantly improved overall survival (8.5 months) compared to gemcitabine alone (6.7 months), with a hazard ratio for death of 0.72, indicating a 28% reduction in the risk of death.

The combination therapy also resulted in better progression-free survival (5.5 months vs. 3.7 months) and a higher overall response rate (23% vs. 7%), although it was associated with increased rates of adverse events like neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. Von Hoff, DD., Ervin, T., Arena, FP., et al.[2022]

In a study of 200 pancreatic cancer patients receiving gemcitabine and nanoparticle albumin-bound paclitaxel, treatment suspension occurred in 61% of cases, primarily due to severe neutropenia (grade 3/4) in 83.6% of patients.

Low baseline platelet counts and age over 65 were identified as risk factors for treatment suspension, while initiating treatment with a dose reduction helped prevent severe neutropenia and allowed for better management of the chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of risk factors related to administration suspension and severe neutropenia in gemcitabine and nab-paclitaxel treatment. Saito, Y., Takekuma, Y., Kobayashi, M., et al.[2022]

The study demonstrates that using ultrasound targeted microbubble destruction (UTMD) to deliver a microbubble-liposome complex (IRMB-OxLipo) containing irinotecan and oxaliplatin significantly reduces tumor size in pancreatic cancer models, with treated tumors being 136% smaller than those receiving the same drugs through conventional delivery methods.

This approach enhances the effectiveness of the FOLFIRINOX chemotherapy regimen, suggesting that UTMD could improve treatment outcomes for patients with pancreatic cancer, which has historically had very low survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An ultrasound responsive microbubble-liposome conjugate for targeted irinotecan-oxaliplatin treatment of pancreatic cancer. Gao, J., Nesbitt, H., Logan, K., et al.[2021]

In a study using an orthotopic xenograft mouse model of pancreatic cancer, combining sonoporation with gemcitabine significantly reduced primary tumor volumes compared to control groups, indicating enhanced drug delivery.

This combination therapy also led to a median survival increase of up to 10%, suggesting that sonoporation could provide additional clinical benefits for patients receiving gemcitabine for pancreatic adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft. Kotopoulis, S., Delalande, A., Popa, M., et al.[2022]

Ultrasound-mediated chemotherapy using paclitaxel-loaded nanoemulsions showed promising efficacy against pancreatic ductal adenocarcinoma (PDA) in a mouse model, particularly in gemcitabine-resistant tumors, suggesting a potential new treatment strategy.

Despite the initial success in reducing tumor growth and metastases, tumors eventually relapsed and developed resistance to paclitaxel, highlighting the need for improved drug delivery methods to ensure uniform distribution within the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasonic nanotherapy of pancreatic cancer: lessons from ultrasound imaging. Rapoport, N., Kennedy, AM., Shea, JE., et al.[2023]

The study introduces a novel method for creating microbubbles that can effectively deliver gemcitabine and paclitaxel to pancreatic cancer cells, showing significant reductions in cell viability in laboratory models.

In mouse models, the new microbubble formulations led to a 40% reduction in tumor size compared to traditional free drug treatments, suggesting improved efficacy and potential for better clinical outcomes in pancreatic cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of a gemcitabine-modified phospholipid and its subsequent incorporation into a single microbubble formulation loaded with paclitaxel for the treatment of pancreatic cancer using ultrasound-targeted microbubble destruction. Logan, KA., Nesbitt, H., Callan, B., et al.[2022]

The study developed a new delivery system using ultrasound-targeted microbubble destruction (UTMD) to enhance the delivery of gemcitabine and a miR-21 inhibitor, showing significantly improved cellular uptake and anticancer effects in pancreatic cancer cells.

In vivo results demonstrated that this co-delivery system led to a substantial reduction in tumor volume and increased blood flow in pancreatic tumors, indicating its potential as an effective treatment strategy for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy. Lin, L., Fan, Y., Gao, F., et al.[2022]

References

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

Phase I/II Trial to Evaluate the Efficacy and Safety of Nanoparticle Albumin-Bound Paclitaxel in Combination With Gemcitabine in Patients With Pancreatic Cancer and an ECOG Performance Status of 2. [2022]

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

nab-Paclitaxel for the treatment of pancreatic cancer. [2023]

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

An in vitro and in vivo study of gemcitabine-loaded albumin nanoparticles in a pancreatic cancer cell line. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer. [2022]

5. Japan pubmed.ncbi.nlm.nih.gov

[Nab-Paclitaxel plus Gemcitabine Hydrochloride in Patients with Metastatic or Recurrent Pancreatic Cancer - A Single Institution Experience]. [2022]

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

New agents in gastrointestinal malignancies: Part 1: Irinotecan in clinical practice. [2019]

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

Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Detection of risk factors related to administration suspension and severe neutropenia in gemcitabine and nab-paclitaxel treatment. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

An ultrasound responsive microbubble-liposome conjugate for targeted irinotecan-oxaliplatin treatment of pancreatic cancer. [2021]

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

Sonoporation-enhanced chemotherapy significantly reduces primary tumour burden in an orthotopic pancreatic cancer xenograft. [2022]

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

Ultrasonic nanotherapy of pancreatic cancer: lessons from ultrasound imaging. [2023]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Synthesis of a gemcitabine-modified phospholipid and its subsequent incorporation into a single microbubble formulation loaded with paclitaxel for the treatment of pancreatic cancer using ultrasound-targeted microbubble destruction. [2022]

13. Australia pubmed.ncbi.nlm.nih.gov

UTMD-Promoted Co-Delivery of Gemcitabine and miR-21 Inhibitor by Dendrimer-Entrapped Gold Nanoparticles for Pancreatic Cancer Therapy. [2022]