Drug Screening Using IMD for Bladder Cancer

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Brigham and Women's Hospital

Disqualifiers: Active infection, Heart failure, Angina, Arrhythmia, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different cancer drugs interact with bladder cancer cells using tiny implantable devices (IMD) that release very small doses of the drugs directly into tumors. The goal is to identify which drugs are most effective against the cancer cells. This study targets individuals with localized bladder cancer who plan to undergo surgery and have a tumor at least 1 cm in size. Participants will have up to four microdevices placed in their tumors to test various drug responses. After a few days, the devices and some tissue will be removed to assess safety and side effects. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

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

What prior data suggests that this implantable micro-device is safe for bladder cancer treatment?

Research shows that tiny devices placed directly into tumors are being tested for safety and effectiveness in treating bladder cancer. These devices release very small amounts of cancer drugs directly into the tumor, and studies have found them to be generally well-tolerated. The doses used are much smaller than those in regular treatments, reducing side effects.

The tests primarily focus on ensuring the safe insertion and removal of the devices. The goal is to minimize safety issues, and reports of serious harmful side effects have been few. The studies aim for minimal complications and successful device placement in most patients.

As this device remains in the early testing stages, researchers continue to gather safety data. However, the use of low drug doses and careful patient monitoring suggests a cautious approach to safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it uses an Implantable Micro-Device (IMD) to screen drugs directly in bladder cancer tissue. Unlike traditional treatments that require systemic administration, this innovative technique allows multiple drugs to be tested simultaneously within the tumor, providing immediate feedback on their effectiveness. This method not only personalizes treatment by identifying the most effective drugs for each patient but also minimizes unnecessary exposure to ineffective therapies. Ultimately, the IMD approach has the potential to revolutionize how bladder cancer treatments are selected and applied, offering a more tailored and efficient path to patient care.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that tiny devices placed inside the body can test how well different cancer drugs work directly in the tumor. In this trial, participants will receive such a microdevice, which releases tiny amounts of various drugs into bladder cancer tissue. Early results suggest this method could help doctors choose the best treatment for each patient. While the device is new, the drugs it releases, like Avelumab and Cisplatin, have proven effective in treating bladder cancer in other studies. For instance, Avelumab was linked to longer survival in some bladder cancer patients. This approach allows for personalized testing of multiple drugs, potentially leading to more effective treatment plans. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with localized bladder cancer, ready for cystectomy, and have a tumor at least 1cm big. They must understand the study and consent to it, be medically stable for procedures, meet certain blood test criteria, and agree to genetic testing. Those with uncontrolled illnesses or bleeding disorders that increase surgery risks can't join.

Inclusion Criteria

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

Patients must be agree to remain abstinent or use contraceptive measures for the duration of the study period

A cancer specialist has reviewed my case to decide on the best treatment plan.

Exclusion Criteria

I do not have a bleeding or clotting disorder that makes surgery risky.

I do not have any severe illnesses that would make surgery or biopsy unsafe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Microdevice Implantation

Implantation of microdevices into the tumor to release microdoses of cancer drugs

48 hours

1 visit (in-person)

Microdevice Removal and Analysis

Removal of microdevices and surrounding tissue for pathologic and molecular analysis

72 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after device removal

6 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The study tests microdoses of various cancer drugs delivered directly into the tumor via implantable microdevices. After about three days, devices are removed along with some tissue for analysis. The aim is to see how different drugs affect the tumor in a very localized way without affecting other body parts.

How Is the Trial Designed?

Group I: DRUG SCREENING USING IMD IN BLADDER CANCER Experimental Treatment 21 Interventions

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

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Urothelial carcinoma, the most common urological cancer, is primarily treated with Bacillus Calmette-Guerin (BCG) immunotherapy for superficial cases and cisplatin-based chemotherapy for metastatic disease, with vinflunine as the standard second-line option in Europe.

Novel PD-1/PD-L1 inhibitors like atezolizumab, nivolumab, and pembrolizumab have shown promise in treating bladder cancer, particularly for patients who cannot tolerate cisplatin, and are generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. Büchler, T.[2019]

In a study of 319 patients with locally advanced bladder cancer, those treated with dose dense MVAC chemotherapy showed a significantly higher rate of complete pathological response (ypT0N0) compared to those treated with gemcitabine and cisplatin (28.0% vs 14.6%).

Patients receiving dose dense MVAC also had better overall survival rates, with a mean survival of 7.0 years compared to 4.2 years for those on gemcitabine and cisplatin, indicating that dose dense MVAC may be a more effective neoadjuvant treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy. Zargar, H., Shah, JB., van Rhijn, BW., et al.[2022]

Bladder cancer, often linked to environmental and lifestyle factors, shows promising outcomes with early intervention; 87% of early-stage patients can achieve 10-year survival after appropriate treatment, although many still require radical cystectomy.

Recent studies suggest that the gemcitabine and cisplatin regimen is as effective as traditional chemotherapy with less toxicity, making it the new standard for advanced bladder cancer treatment in ongoing phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder cancer. Patton, SE., Hall, MC., Ozen, H.[2022]

Avelumab, an anti-PD-L1 antibody, has demonstrated clinical efficacy and a well-tolerated safety profile in treating metastatic and advanced urothelial carcinoma (UC) after platinum-based chemotherapy failure, leading to its FDA approval as a second-line treatment.

The mechanism of action for avelumab includes inducing antibody-dependent cellular cytotoxicity (ADCC), which helps in effectively targeting and destroying tumor cells, and it is currently being evaluated in ongoing trials for maintenance therapy and in combination with chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which place for avelumab in the management of urothelial carcinoma? Larroquette, M., Gross-Goupil, M., Daste, A., et al.[2020]

In a study involving 71 patients with metastatic urothelial cancer (mUC) who were ineligible for cisplatin-based chemotherapy, avelumab demonstrated a median overall survival of 10 months, with 43% of patients alive at one year, indicating its efficacy as a first-line treatment option.

Avelumab was found to be safe, with adverse events occurring in 49.3% of patients, but no treatment-related deaths were reported, suggesting it is a tolerable option for patients who cannot receive traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line avelumab for patients with PD-L1-positive metastatic or locally advanced urothelial cancer who are unfit for cisplatin. Iacovelli, R., Ciccarese, C., Brunelli, M., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06204614

Drug Screening Using IMD in Bladder Cancer The implantable microdevice will release microdoses of specific drugs or drug combinations as a possible tool to evaluate the effectiveness of several cancer ...

2. mdpi.com mdpi.com/2076-3417/15/17/9304

Battery-Free Innovation: An RF-Powered Implantable ... This study presents the development of an innovative battery-free, RF-powered implantable microdevice designed for intravesical chemotherapy ...

3. researchgate.net researchgate.net/publication/394922446_Battery-Free_Innovation_An_RF-Powered_Implantable_Microdevice_for_Intravesical_Chemotherapy

Battery-Free Innovation: An RF-Powered Implantable ... This study presents the development of an innovative battery-free, RF-powered implantable microdevice designed for intravesical chemotherapy ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1076633224005737

Multi-DECT Image-based Intratumoral and Peritumoral ... A study by Evrimler et al (37). suggests that utilizing this new method for HV detection in bladder cancer patients can enhance the likelihood of an optimal ...

5. auajournals.org auajournals.org/doi/10.1097/JU.0000000000004337

Editor's Choice Given in 6 weekly intravesical instillations, UGN-102 led to an 80% complete response rate at 3 months, with an impressive 82% probability of ...

6. cancer.gov cancer.gov/clinicaltrials/NCI-2024-00633

Implantable Microdevice for Evaluation of Drug Response ... This early phase I trial tests the safety and feasibility of an implantable microdevice for the evaluation of drug response in patients with bladder cancer ...

7. dana-farber.org dana-farber.org/clinical-trials/23-269

Pilot study of an implantable microdevice for in situ ... 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 ...

8. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/450335

Drug Screening Using IMD in Bladder Cancer The implantable microdevice will release microdoses of specific drugs or drug combinations as a possible tool to evaluate the effectiveness of several cancer ...

9. kcrs.kidneycan.org kcrs.kidneycan.org/wp-content/uploads/2024/07/29_Wenxin_Xu.pdf

Pilot study of an implantable microdevice for in vivo ... The primary endpoints of this study are safety, defined as ≤ 2 safety failures, and feasibility, defined as ≥ 16 successful IMD implantations with interpretable.