Drug Screening Using IMD in Bladder Cancer

NCT06204614 | Unknown Early Phase 1 DMC FDA Drug FDA Device

• 1 other identifier: 23-269
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Muscle Invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• Safety of microdevice placement and removal based on assessment of adverse events

  A device will be declared safe if and only if all implanted devices do not cause an adverse event as defined in section 5.4. The device will be declared safe if 2 or less unacceptable toxicities are observed. Safety will be monitored using a BOIN-based boundary estimated assuming a 10% event rate and a stopping probability of 0.70. The boundary will not take effect until the third patient is enrolled. The trial will be stopped for safety concerns if the investigators see at least 1 adverse event in the first nine patients, or 2 adverse events across all 18. The probability of seeing 2 or less unacceptable toxicity events is 71% if the true rate of toxicity is 10% and 94% if the true rate of toxicity is 5%. The safety estimate will be summarized as number, percentage and with a 95% binomial confidence interval

  From the time of arrival to interventional radiology for microdevice placement up to 6 weeks.

• Feasibility of microdevice placement

  A placement is defined as successful if the investigators can implant and extract at least one microdevice from a patient's tumor with readable tissue for pathology from at least three-quarters of the device reservoirs surrounded by at least 400um of surrounding tissue. The investigators will declare feasibility if the lower bound of the 95% binomial CI does not exceed 0.65, that is if the investigators have 2 or fewer failures. The number of patients with successful retrieval will be summarized as number, percentage and with a 95% CI. Based on prior studies, if device reservoirs are surrounded by at least 400um of tissue, this enables downstream multi-omic analysis.

  48 Hours

Secondary Outcomes (2)

• Local intratumor response

  48 Hours

• Exploration of additional potential biomarkers of drug response

  48 Hours

Study Arms (1)

DRUG SCREENING USING IMD IN BLADDER CANCER

EXPERIMENTAL

Study participants placed in arm 1 will be implanted with the microdevice.

Device: Implantable Micro-Device; Drug: Methotrexate; Drug: Carboplatin; Drug: Avelumab; Drug: Paclitaxel; Drug: Vinblastine; Drug: Gemcitabine/Cisplatin I; Drug: Methotrexate/Vinblastine/Doxorubicin/Cisplatin/Avelumab; Drug: Gemcitabine/Cisplatin II; Drug: Cisplatin; Drug: Nivolumab; Drug: Pembrolizumab; Drug: Gemcitabine/Carboplatin; Drug: Methotrexate/Vinblastine/Doxorubicin/Cisplatin; Drug: Gemcitabine/Cisplatin/Nivolumab; Drug: Erdafitinib; Drug: Paclitaxel/Docetaxel/Ifosfamide; Drug: Gemcitabine; Drug: Gemcitabine/Carboplatin/Nivolumab; Drug: Enfortumab; Drug: Sacituzumab

Interventions

Implantable Micro-Device 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.

DRUG SCREENING USING IMD IN BLADDER CANCER

Methotrexate DRUG

Methotrexate will be placed in reservoir 1 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Carboplatin DRUG

Carboplatin will be placed in reservoir 2 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Avelumab DRUG

Avelumab will be placed in reservoir 3 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Paclitaxel DRUG

Paclitaxel will be placed in reservoir 4 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Vinblastine DRUG

Vinblastine will be placed in reservoir 5 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Gemcitabine/Cisplatin I DRUG

Gemcitabine/Cisplatin will be placed in reservoir 6 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Methotrexate/Vinblastine/Doxorubicin/Cisplatin/Avelumab DRUG

(Methotrexate/Vinblastine/Doxorubicin/Cisplatin/Avelumab) will be placed in reservoir 7 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Gemcitabine/Cisplatin II DRUG

Gemcitabine/Cisplatin will be placed in reservoir 8 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Cisplatin DRUG

Cisplatin will be placed in reservoir 9 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Nivolumab DRUG

Nivolumab will be placed in reservoir 10 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Pembrolizumab DRUG

Pembrolizumab will be placed in reservoir 11 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Gemcitabine/Carboplatin DRUG

Gemcitabine/Carboplatin will be placed in reservoir 12 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Methotrexate/Vinblastine/Doxorubicin/Cisplatin DRUG

(Methotrexate/Vinblastine/Doxorubicin/Cisplatin) will be placed in reservoir 13 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Gemcitabine/Cisplatin/Nivolumab DRUG

(Gemcitabine/Cisplatin/Nivolumab) will be placed in reservoir 14 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Erdafitinib DRUG

Erdafitinib will be placed in reservoir 15 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Paclitaxel/Docetaxel/Ifosfamide DRUG

(Paclitaxel/Docetaxel/Ifosfamide) will be placed in reservoir 16 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Gemcitabine DRUG

Gemcitabine will be placed in reservoir 17 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Gemcitabine/Carboplatin/Nivolumab DRUG

(Gemcitabine/Carboplatin/Nivolumab) will be placed in reservoir 18 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Enfortumab DRUG

Enfortumab will be placed in reservoir 19 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Sacituzumab DRUG

Sacitzumab will be placed in reservoir 20 of the implantable microdevice.

DRUG SCREENING USING IMD IN BLADDER CANCER

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

Methotrexate; Carboplatin; avelumab; Paclitaxel; Vinblastine; Gemcitabine; Cisplatin; Nivolumab; pembrolizumab; erdafitinib; enfortumab vedotin; sacituzumab govitecan

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Laboratory for Bio-Micro-Devices

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: January 12, 2024
• Study Start: February 14, 2024
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2025
• Last Updated: January 12, 2024

Record last verified: 2024-01

Locations

US (1)