Drug Screening Using IMD in Bladder Cancer

Официальное название

Pilot Study of an Implantable Microdevice for in Situ Evaluation of Drug Response in Primary Bladder Tumors

Обзор

This research study involves implanting up to 4 microdevices, each small enough to fit inside the tip of a needle, into a tumor. These devices will release microdoses (many thousands of times less than a treatment dose) of different cancer drugs into the tumor. After approximately 72 hours, the devices and small regions of surrounding tissue will be removed and studied. There will be a follow-up visit within 42 days of device removal to assess for potential safety issues or side effects.

Подробное описание

This is a phase I pilot study of microdevice implantation and retrieval in patients with primary bladder cancer. The microdevice is 5x1mm and can be deployed using a biopsy needle placed percutaneously using imaging guidance. The purpose of the microdevice is to measure local intratumor response to antitumor medications in patients with primary bladder cancer. The microdevice contains multiple, separate reservoirs that are each loaded with a specific drug or drug combination.

Candidate patients will first be evaluated based on a CT or MRI, obtained as part of clinical care, and a physician who will determine whether the target lesion is amenable for microdevice implantation. Microdevice implantation will occur via cystoscopy using a flexible grasper (similar to that used for ureteral stent removal). Several independent microdevices will be placed per patient and target lesion. After implantation, the reservoirs release microdoses of each drug allowing the drug to interact with the tumor tissue in its native microenvironment. After device removal and before pathologic analysis, a repeat plain film X-ray of the bladder will be obtained to evaluate for microdevice migration. The microdevice(s) will be removed along with the target tumor as part of standard-of-care surgical excision. The tumor tissue surrounding the device will undergo pathologic and molecular analysis to assess local drug efficacy for each reservoir. These analyses will explore the impact of drug treatment on local cellular processes (e.g., apoptosis, pathway signaling).

The investigators will also investigate preliminary correlations between drug response as assessed by the microdevice and clinical outcomes and response to therapy. Collectively, these studies will establish the feasibility of clinical application of a drug-sensitivity microdevice in bladder cancer and the capacity of such a device to predict systemic response to cancer therapeutics.

Вмешательства

• Устройство Implantable Micro-Device
  The implantable microdevice will release microdoses of specific drugs or drug combinations as a possible tool to evaluate the effectiveness of several cancer drugs against bladder cancer.
• Препарат Methotrexate
  Methotrexate will be placed in reservoir 1 of the implantable microdevice.
• Препарат Carboplatin
  Carboplatin will be placed in reservoir 2 of the implantable microdevice.
• Препарат Avelumab
  Avelumab will be placed in reservoir 3 of the implantable microdevice.
• Препарат Paclitaxel
  Paclitaxel will be placed in reservoir 4 of the implantable microdevice.
• Препарат Vinblastine
  Vinblastine will be placed in reservoir 5 of the implantable microdevice.
• Препарат Gemcitabine/Cisplatin I
  Gemcitabine/Cisplatin will be placed in reservoir 6 of the implantable microdevice.
• Препарат Methotrexate/Vinblastine/Doxorubicin/Cisplatin/Avelumab
  (Methotrexate/Vinblastine/Doxorubicin/Cisplatin/Avelumab) will be placed in reservoir 7 of the implantable microdevice.
• Препарат Gemcitabine/Cisplatin II
  Gemcitabine/Cisplatin will be placed in reservoir 8 of the implantable microdevice.
• Препарат Cisplatin
  Cisplatin will be placed in reservoir 9 of the implantable microdevice.

Первичные конечные точки

• Safety of microdevice placement and removal based on assessment of adverse events [Срок оценки: From the time of arrival to interventional radiology for microdevice placement up to 6 weeks.]
• Feasibility of microdevice placement [Срок оценки: 48 Hours]

Вторичные конечные точки (2)

• Local intratumor response [Срок оценки: 48 Hours]
• Exploration of additional potential biomarkers of drug response [Срок оценки: 48 Hours]

Критерии участия

Критерии включения

• Patients must have the ability to understand and the willingness to sign a written informed consent document.
• Participants must have confirmed clinically localized bladder cancer with histology of urothelial cell carcinoma or variant histology and radiographic imaging consistent with stage T2-T3 N0 disease. Patients must be planned for cystectomy as part of their clinical care. The lesion planned for excision must be at least 1cm in size.
• Participants must be 18 years of age or older. Patients must have the ability to understand and the willingness to sign a written informed consent document.
• Participants must have confirmed clinically localized bladder cancer with histology of urothelial cell carcinoma or variant histology and radiographic imaging consistent with stage T2-T3 N0 disease. Patients must be planned for cystectomy as part of their clinical care. The lesion planned for excision must be at least 1cm in size.
• Participants must be 18 years of age or older. Patients must have the ability to understand and the willingness to sign a written informed consent document.
• Participants must have confirmed clinically localized bladder cancer with histology of urothelial cell carcinoma or variant histology and radiographic imaging consistent with stage T2-T3 N0 disease. Patients must be planned for cystectomy as part of their clinical care. The lesion planned for excision must be at least 1cm in size.
• Participants must be 18 years of age or older.
• Participants must be evaluated by a medical oncologist who will determine the clinically appropriate treatment strategy based on clinical history and extent of disease.
• Patients must be deemed medically stable to undergo both percutaneous procedures and standard-of-care surgical procedures.
• Participants will undergo laboratory testing within 30 days prior to the procedure (or within 72 hours if there has been a change in the clinical status since the initial blood draw). Patients must have absolute neutrophil count ≥1,000/mcL, platelets ≥50,000/mcL, PT (INR) 1.5 and PTT<1.5x control.
• Participants must have undergone CT or MRI that assesses the extent of disease and allows the research team to assess for study eligibility. This will have been done as part of the standard-of-care.
• The participant's case must be reviewed by the treating physician to assess the following factors:

• Patient is clinically stable to undergo microdevice implantation and surgical procedures
• Patient has sufficient volume of disease to allow implantation of the microdevice
• Patient has a lesion for which the microdevice is a) amenable to percutaneous placement, and b) amenable to removal at the time of surgery
• Patients must be willing to undergo research-related genetic sequencing (somatic and germline) and data management, including the deposition of de-identified genetic sequencing data in NIH central data repositories.
• Patients must be agree to remain abstinent or use contraceptive measures for the duration of the study period

Критерии исключения

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit the safety of a biopsy and/or surgery.
• Uncorrectable bleeding or coagulation disorder known to cause increased risk with surgical or biopsy procedures (detailed below in section 5.1.2.1).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Brigham and Women's Hospital — Boston

Идентификаторы

NCT: NCT06204614 · 23-269

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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