Drug Delivery Microdevice for Sarcoma

Overseen By Joseph A Ludwig, MD

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: High surgical risk, Pregnancy, Lactation, others

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

Compensation: Varies

Number of Visits: 2

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This early phase I trial studies the side effects of implanting and removing a microdevice in patients with sarcomas that have spread to other places in the body (metastatic) or have come back (recurrent). Microdevices are rice-sized devices that are implanted into tumor tissue and are loaded with 10 different drugs that are delivered at very small doses, or "microdoses," which may only affect a very small, local area inside the tumor. The purpose of this study is to determine which drugs delivered in the microdevice affect tumor tissue in patients with sarcomas.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of this drug for treating sarcoma?

Research shows that drug delivery systems, including microdevices, have significantly improved cancer treatments by allowing controlled and localized delivery of drugs, which can enhance their effectiveness and reduce side effects. Additionally, studies indicate that delivering cancer drugs directly into tumors can help determine their effectiveness, potentially improving patient outcomes. ^{1 2 3 4 5}

Is the Drug Delivery Microdevice for Sarcoma generally safe for humans?

The reviewed research suggests that new drug delivery methods, like the Drug Delivery Microdevice, aim to reduce toxicity by targeting drugs directly to tumors, minimizing side effects. These methods are being explored to improve safety and effectiveness in treating sarcomas. ^{6 7 8 9 10}

How does the Drug Delivery Microdevice treatment for sarcoma differ from other treatments?

The Drug Delivery Microdevice for sarcoma is unique because it allows for localized delivery of drugs directly to the tumor site, minimizing systemic side effects and improving drug effectiveness. This approach contrasts with traditional systemic chemotherapy, which can have widespread side effects and limited tumor penetration. ^{5 11 12 13 14}

Research Team

Joseph A. Ludwig

Principal Investigator

The University of Texas MD Anderson Cancer Center

Eligibility Criteria

This trial is for people aged 10 or older with sarcoma that has spread or returned, and who need surgery as part of their treatment. They must be able to perform daily activities (ECOG <=2) and consent to participate. It's not for those under 10, pregnant or breastfeeding women, patients refusing surgery, or with allergies to drugs in the microdevice.

Inclusion Criteria

My sarcoma has returned or spread and surgery is recommended.

Documented, signed, dated informed consent to participate in the microdevice study

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

I am younger than 10 years old.

I do not want or cannot have surgery for my condition.

You are allergic to any of the drugs used in the microdevice.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Microdevice Implantation

Patients undergo percutaneous implantation of up to 3 drug delivery microdevices up to 2 days before standard of care surgery

2 days

1 visit (in-person)

Surgery and Microdevice Removal

At the time of surgery 2 days later, patients have the drug delivery microdevice(s) removed

2 days

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year

Treatment Details

Interventions

• Doxorubicin
• Doxorubicin Hydrochloride
• Drug Delivery Microdevice
• Everolimus
• Ganitumab
• Ifosfamide
• Irinotecan
• Pazopanib
• Polyethylene Glycol
• Temozolomide
• Temsirolimus
• Vincristine

Trial Overview The study tests a tiny implantable device containing microdoses of various drugs like Doxorubicin and Everolimus directly into sarcoma tumors. The goal is to see which drugs affect tumor tissue when delivered through this new method during standard surgical care.

Participant Groups

Group I: Device Feasibility (microdevice, surgery) Experimental Treatment 13 Interventions

Patients undergo percutaneous implantation of up to 3 drug delivery microdevices up to 2 days before standard of care surgery. Patients receive doxorubicin hydrochloride, ifosfamide, vincristine, irinotecan, temozolomide, pazopanib, everolimus, polyethylene glycol, ganitumab, and temsirolimus via the microdevice in the absence of unacceptable toxicity. At the time of surgery 2 days later, patients have the drug delivery microdevice(s) removed.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Two innovative devices have been developed to deliver cancer drugs directly into tumors, which can help determine how sensitive a tumor is to specific treatments.

If these devices are used in clinical practice, they could lead to more targeted cancer therapies, improving patient survival rates while minimizing unnecessary side effects from indiscriminate drug use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug testing in the patient: toward personalized cancer treatment. Coombes, RC.[2018]

Innovative implantable drug delivery devices are being developed to effectively administer biologics, gene therapies, and small molecules that cannot be taken orally or through other common methods, ensuring direct delivery to the treatment site.

Recent advancements in microtechnologies have led to the creation of MEMS-enabled micropumps that can provide precise, on-demand drug delivery, showing promise in preclinical studies for applications like cancer treatment and chronic ocular dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MEMS-enabled implantable drug infusion pumps for laboratory animal research, preclinical, and clinical applications. Meng, E., Hoang, T.[2021]

The study explored a new method of microinjecting multiple drugs into sarcomas to assess their pharmacodynamic responses after tumor resection, which could help evaluate the effectiveness of anticancer treatments.

This innovative approach may provide valuable insights into how well different anticancer agents work in human tumors, potentially leading to more effective cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bridging the Translational Divide in Oncology: In Vivo Testing of Chemo-sensitivity. Sleijfer, S., Lolkema, M.[2021]

Drug delivery systems for cancer treatments have been widely used and have improved both new and existing therapies, benefiting millions of patients.

Current systems include various methods like controlled delivery, local chemotherapy, and liposomal systems, while future innovations may involve 'smart' delivery methods like controlled release microchips.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advancing the field of drug delivery: taking aim at cancer. Moses, MA., Brem, H., Langer, R.[2019]

The development of miniaturized drug delivery microdevices offers new opportunities for treating both acute and chronic conditions by allowing precise control over drug release and pharmacokinetics.

These microdevices can enhance treatment adherence and effectiveness, particularly in complex clinical scenarios like cancer and hemorrhagic shock, potentially leading to improved clinical outcomes and significant social benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of biomedical microdevices for controlled drug delivery. Gurman, P., Miranda, OR., Clayton, K., et al.[2015]

Combining new targeted therapies with conventional chemotherapy may enhance tumor-killing effects while reducing toxicity and the risk of drug resistance in sarcoma treatment.

Innovative drug delivery methods, such as metronomic scheduling and isolated limb perfusion, allow for higher concentrations of therapeutic agents to be administered directly to tumors, minimizing systemic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experimental approaches to treatment of soft tissue sarcoma. Hwang, RF., Hunt, KK.[2019]

The study demonstrated that a chimeric polypeptide doxorubicin (CP-Dox) formulation was more effective than free doxorubicin in treating malignant peripheral nerve sheath tumors (MPNSTs), showing increased drug retention and elevated CD8+ T cell levels.

However, in undifferentiated pleomorphic sarcoma (UPS) models, CP-Dox did not improve survival compared to free doxorubicin, indicating that the effectiveness of nanoparticle-encapsulated chemotherapy can vary significantly depending on the specific tumor subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in Pten-deleted Mouse Models of Sarcoma. Dodd, RD., Scherer, A., Huang, W., et al.[2023]

Sarcomas are complex tumors that are difficult to treat, often requiring a team of specialists, and are associated with chronic inflammation, which plays a significant role in their development.

Recent advancements in targeted therapies, including the use of oncolytic viruses and anti-inflammatory nutraceuticals, show promise in interrupting key signaling pathways involved in sarcoma growth, potentially leading to less toxic treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of inflammation in sarcoma. Radons, J.[2016]

A review of 238 phase I and II clinical trials for sarcomas revealed that only 5% led to phase III trials, with the majority of successful trials being funded by industry, highlighting the importance of industry support in advancing sarcoma treatments.

Most trials tested drugs not originally developed for sarcoma (about 90%) and often combined different sarcoma subtypes in studies, which may limit the understanding of drug efficacy across specific sarcoma types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development. Lee, DY., Staddon, AP., Shabason, JE., et al.[2021]

Novel therapies in sarcoma treatment can significantly enhance quality of life and improve outcomes for high-risk patients, with various options tailored to specific types of sarcomas.

Innovative local control measures, such as embolization and thermal ablation, are crucial for effectively managing tumors and metastases, contributing to better symptom control and reduced side effects from traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic approaches in pediatric and young adult sarcomas. Anderson, PM., Pearson, M.[2019]

A novel drug-loaded arrowhead array device (AAD) was developed using 3D printing technology to deliver chemotherapy directly to the surgical site, which significantly reduced local recurrence of cancer after surgery in murine models.

The AAD not only improved survival rates but also has the potential for personalization in clinical applications, enhancing the effectiveness of chemotherapy while minimizing systemic toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

3D printed drug-loaded implantable devices for intraoperative treatment of cancer. Hagan, CT., Bloomquist, C., Warner, S., et al.[2023]

The AC electrothermal (ACET) micromixer developed in this study achieved a high mixing efficiency of 89.12% at a voltage of 3V and frequency of 500 kHz, making it effective for delivering uniform drug concentrations to tumor cells.

When tested with tamoxifen on human breast cancer cells (MCF-7) over five days, the micromixer demonstrated potential for enhancing drug delivery and promoting rapid tumor cell death, indicating its usefulness in organ-on-a-chip systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-plane microvortices micromixer-based AC electrothermal for testing drug induced death of tumor cells. Lang, Q., Ren, Y., Hobson, D., et al.[2020]

A microelectromechanical systems (MEMS) device effectively delivered the chemotherapeutic agent BCNU directly to tumors in rats, showing a dose-dependent inhibition of tumor growth with doses ranging from 0.67 to 2 mg.

The MEMS device demonstrated similar effectiveness to traditional subcutaneous injections of BCNU, and its design allows for precise control over the release of multiple therapeutic agents, suggesting potential for enhanced combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo delivery of BCNU from a MEMS device to a tumor model. Li, Y., Ho Duc, HL., Tyler, B., et al.[2019]

Microneedle-based delivery systems are gaining attention for their ability to locally implant therapeutics directly into tumor tissue, which helps avoid complications associated with systemic drug delivery.

These devices can effectively deliver a range of therapeutic agents, including chemotherapeutics and vaccines, potentially enhancing the effectiveness of cancer treatments by improving drug penetration into tumor tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microneedle-based delivery devices for cancer therapy: A review. Moreira, AF., Rodrigues, CF., Jacinto, TA., et al.[2020]

References

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

Drug testing in the patient: toward personalized cancer treatment. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

MEMS-enabled implantable drug infusion pumps for laboratory animal research, preclinical, and clinical applications. [2021]

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

Bridging the Translational Divide in Oncology: In Vivo Testing of Chemo-sensitivity. [2021]

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

Advancing the field of drug delivery: taking aim at cancer. [2019]

5. England pubmed.ncbi.nlm.nih.gov

Clinical applications of biomedical microdevices for controlled drug delivery. [2015]

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

Experimental approaches to treatment of soft tissue sarcoma. [2019]

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

Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in Pten-deleted Mouse Models of Sarcoma. [2023]

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

The role of inflammation in sarcoma. [2016]

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

Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development. [2021]

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

Novel therapeutic approaches in pediatric and young adult sarcomas. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

3D printed drug-loaded implantable devices for intraoperative treatment of cancer. [2023]

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

In-plane microvortices micromixer-based AC electrothermal for testing drug induced death of tumor cells. [2020]

13. Netherlands pubmed.ncbi.nlm.nih.gov

In vivo delivery of BCNU from a MEMS device to a tumor model. [2019]

14. Netherlands pubmed.ncbi.nlm.nih.gov

Microneedle-based delivery devices for cancer therapy: A review. [2020]