Drug Delivery Microdevice for Sarcoma
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: M.D. Anderson Cancer Center
Disqualifiers: High surgical risk, Pregnancy, Lactation, others
No Placebo Group
Breakthrough Therapy
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.
12345Is 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.
678910How 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.
511121314Eligibility 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.
+1 more
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.
+1 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Device Feasibility (microdevice, surgery)Experimental Treatment13 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
M D Anderson Cancer CenterHouston, TX
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
MEMS-enabled implantable drug infusion pumps for laboratory animal research, preclinical, and clinical applications. [2021]Innovation in implantable drug delivery devices is needed for novel pharmaceutical compounds such as certain biologics, gene therapy, and other small molecules that are not suitable for administration by oral, topical, or intravenous routes. This invasive dosing scheme seeks to directly bypass physiological barriers presented by the human body, release the appropriate drug amount at the site of treatment, and maintain the drug bioavailability for the required duration of administration to achieve drug efficacy. Advances in microtechnologies have led to novel MEMS-enabled implantable drug infusion pumps with unique performance and feature sets. In vivo demonstration of micropumps for laboratory animal research and preclinical studies include acute rapid radiolabeling, short-term delivery of nanomedicine for cancer treatment, and chronic ocular drug dosing. Investigation of MEMS actuators, valves, and other microstructures for on-demand dosing control may enable next generation implantable pumps with high performance within a miniaturized form factor for clinical applications.
Drug testing in the patient: toward personalized cancer treatment. [2018]Two different devices show that delivery of cancer drugs directly into tumors in vivo can indicate cancer sensitivity; if implemented in clinical practice, these devices have the potential to reduce indiscriminate drug use, to improve survival, and to reduce unnecessary adverse effects (Jonas et al. and Klinghoffer et al., this issue).
Bridging the Translational Divide in Oncology: In Vivo Testing of Chemo-sensitivity. [2021]A study was presented in which sarcomas were microinjected simultaneously with several drugs to study the pharmacodynamic response after resection. This platform may represent a future way of probing efficacy of anticancer agents in the relevant model system: human tumors.See related article by Gundle et al., p. 3958.
Advancing the field of drug delivery: taking aim at cancer. [2019]Drug delivery systems for cancer therapeutics have now been used by millions of patients and have resulted in the creation of new therapies as well as significantly improving existing ones. Here we discuss a number of the drug delivery systems that have been approved by regulatory authorities and that are currently in clinical use, such as controlled delivery of cancer therapeutics, local chemotherapy, polymer drug conjugates, liposomal systems, and transdermal drug delivery patches. The next generation of "smart" drug delivery approaches such as controlled release microchips are discussed as are some of the future challenges and directions in this field.
Clinical applications of biomedical microdevices for controlled drug delivery. [2015]Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine.
Phase I and phase II clinical trials in sarcoma: Implications for drug discovery and development. [2021]There has been limited progress in the development of novel therapeutics for the treatment of sarcomas. A review of phase I and II clinical trials for sarcomas may give insight into factors influencing sarcoma drug development.
Experimental approaches to treatment of soft tissue sarcoma. [2019]The experimental approaches described in this article represent potential new approaches for targeted therapy. Thus far, none of the preclinical data have demonstrated a cure for sarcomas; however, the antitumor effects of many of these new agents seem to be enhanced when the agents are combined with chemotherapeutic agents. The combination of novel therapeutics with conventional chemotherapy may be the most effective strategy in terms of maximization of tumor killing and minimization of toxicity and the risk of drug resistance. Not only are new drugs being developed for treatment of sarcomas but new ways of delivering drugs are also being investigated. The angiogenic, or metronomic, schedule of drug delivery may be preferable to conventional schedules in achieving optimal tumor inhibition. In addition, isolated limb perfusion is a unique approach to delivery of drugs, such as TNF and melphalan, for sarcomas and melanomas [137, 138]. The advantages of this method of drug delivery include the ability to administer therapeutic agents in high concentrations to a specific region of the body without systemic toxicity. Further advances in the understanding of the biology of sarcomas along with novel approaches to delivery of drugs are crucial to the development of new and effective therapies.
Tumor Subtype Determines Therapeutic Response to Chimeric Polypeptide Nanoparticle-based Chemotherapy in Pten-deleted Mouse Models of Sarcoma. [2023]Nanoparticle-encapsulated drug formulations can improve responses to conventional chemotherapy by increasing drug retention within the tumor and by promoting a more effective antitumor immune response than free drug. New drug delivery modalities are needed in sarcomas because they are often chemoresistant cancers, but the rarity of sarcomas and the complexity of diverse subtypes makes it challenging to investigate novel drug formulations.
The role of inflammation in sarcoma. [2016]Sarcomas encompass a heterogenous group of tumors with diverse pathologically and clinically overlapping features. It is a rarely curable disease, and their management requires a multidisciplinary team approach. Chronic inflammation has emerged as one of the hallmarks of tumors including sarcomas. Classical inflammation-associated sarcomas comprise the inflammatory malignant fibrous histiocytoma and Kaposi sarcoma. The identification of specific chromosomal translocations and important intracellular signaling pathways such as Ras/Raf/MAPK, insulin-like growth factor, PI3K/AKT/mTOR, sonic hedgehog and Notch together with the increasing knowledge of angiogenesis has led to development of targeted therapies that aim to interrupt these pathways. Innovative agents like oncolytic viruses opened the way to design new therapeutic options with encouraging findings. Preclinical evidence also highlights the therapeutic potential of anti-inflammatory nutraceuticals as they can inhibit multiple pathways while being less toxic. This chapter gives an overview of actual therapeutic standards, newest evidence-based studies and exciting options for targeted therapies in sarcomas.
Novel therapeutic approaches in pediatric and young adult sarcomas. [2019]Novel therapy as part of sarcoma treatment schemas can enhance quality of life and is important in improving outcomes of high-risk sarcomas. Additional chemotherapy and biotherapy options to reduce tumor burden and prevent metastases include intra-arterial chemotherapy in osteosarcoma; intrapleural chemotherapy, aerosol 9-nitrocamptothecin, or protracted irinotecan and temozolomide in Ewing's sarcoma; continuous hyperthermic peritoneal perfusion for malignancy involving the peritoneum, such as desmoplastic small round cell tumor; and ifosfamide with muramyl tripeptide phosphatidyl ethanolamine liposomes in osteosarcoma. These treatments bring improved control of symptoms, including reduction in nausea, mucositis, cardiotoxicity, and central nervous system toxicity. Portable infusion devices have facilitated introduction of outpatient doxorubicin, ifosfamide, and methotrexate regimens and home-infusion irinotecan. Physical approaches to eliminate sarcoma tumors and metastases are critical for durable responses. Novel local control measures include embolization before surgery, radiosensitization, anti-vascular endothelial growth factor therapy during chemo-radiotherapy, proton therapy, samarium, thermal ablation (radiofrequency ablation), and cryoablation.
Microneedle-based delivery devices for cancer therapy: A review. [2020]Macroscale delivery systems that can be locally implanted on the tumor tissue as well as avoid all the complications associated to the systemic delivery of therapeutics have captured researchers' attention, in recent years. Particularly, the microneedle-based devices can be used to efficiently deliver both small and macro-molecules, like chemotherapeutics, proteins, and genetic material, along with nanoparticle-based anticancer therapies. Such capacity prompted the application of microneedle devices for the development of new anticancer vaccines that can permeate the tumor tissue and simultaneously improve the effectiveness of therapeutic agents. Based on the promising results demonstrated by the microneedle systems in the local administration of anticancer therapeutics, this review summarizes the different microneedle formulations developed up to now aimed for application on cancer therapy (mphasizing those produced with polymers). Additionally, the microneedles' general properties, type of therapeutic approach and its main advantages are also highlighted.
3D printed drug-loaded implantable devices for intraoperative treatment of cancer. [2023]Surgery is an important treatment for cancer; however, local recurrence following macroscopically-complete resection is common and a significant cause of morbidity and mortality. Systemic chemotherapy is often employed as an adjuvant therapy to prevent recurrence of residual disease, but has limited efficacy due to poor penetration and dose-limiting off-target toxicities. Selective delivery of chemotherapeutics to the surgical bed may eliminate residual tumor cells while avoiding systemic toxicity. While this is challenging for traditional drug delivery technologies, we utilized advances in 3D printing and drug delivery science to engineer a drug-loaded arrowhead array device (AAD) to overcome these challenges. We demonstrated that such a device can be designed, fabricated, and implanted intraoperatively and provide extended release of chemotherapeutics directly to the resection area. Using paclitaxel and cisplatin as model drugs and murine models of cancer, we showed AADs significantly decreased local recurrence post-surgery and improved survival. We further demonstrated the potential for fabricating personalized AADs for intraoperative application in the clinical setting.
In-plane microvortices micromixer-based AC electrothermal for testing drug induced death of tumor cells. [2020]Herein, we first describe a perfusion chip integrated with an AC electrothermal (ACET) micromixer to supply a uniform drug concentration to tumor cells. The in-plane fluid microvortices for mixing were generated by six pairs of reconstructed novel ACET asymmetric electrodes. To enhance the mixing efficiency, the novel ACET electrodes with rotating angles of 0°, 30°, and 60° were investigated. The asymmetric electrodes with a rotating angle of 60° exhibited the highest mixing efficiency by both simulated and experimental results. The length of the mixing area is 7 mm, and the mixing efficiency is 89.12% (approximate complete mixing) at a voltage of 3 V and a frequency of 500 kHz. The applicability of our micromixer with electrodes rotating at 60° was demonstrated by the drug (tamoxifen) test of human breast cancer cells (MCF-7) for five days, which implies that our ACET in-plane microvortices micromixer has great potential for the application of drug induced rapid death of tumor cells and mixing of biomaterials in organs-on-a-chip systems.
In vivo delivery of BCNU from a MEMS device to a tumor model. [2019]A drug delivery micrcoelectromechanical systems (MEMS) device was used to locally deliver a chemotherapeutic agent (BCNU) to an experimental tumor in rats. This MEMS device consists of an array of reservoirs etched into the silicon substrate. The drug release is achieved by the electrochemical dissolution of the gold membranes covering the reservoirs. A new Pyrex package was developed to improve the BCNU release kinetics and enhance device capacity. Co-formulation of BCNU with polyethylene glycol (PEG) led to complete and rapid release of drug in vivo. BCNU delivered from the MEMS device showed dose-dependent inhibiting effect on the tumor growth in the BCNU dosage range of 0.67 approximately 2 mg. BCNU delivered from the activated devices was as effective as equipotent subcutaneous injections of BCNU in inhibiting tumor growth. Further optimization using this MEMS device to deliver BCNU in combination with other therapeutic agents against the tumor challenge is possible because of the unique capability of the device to precisely control the temporal release profiles of multiple substances.