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

18 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug Avelumab for bladder cancer?

Avelumab, a PD-L1 inhibitor, has shown effectiveness as a first-line therapy for patients with metastatic urothelial cancer who are not eligible for cisplatin-based chemotherapy, providing an alternative treatment option for these patients. ^{1 2 3 4 5}

Is the treatment generally safe for humans?

Avelumab, a treatment for bladder cancer, has shown a well-tolerated safety profile in clinical studies, with common side effects including fatigue, low white blood cell count, anemia, muscle pain, decreased appetite, and nausea. It is considered relatively safe, especially for patients who cannot tolerate platinum-based treatments. ^{1 3 6 7 8}

What makes the drug Avelumab unique for treating bladder cancer?

Avelumab is unique for treating bladder cancer because it is an immunotherapy drug that targets the PD-1/PD-L1 pathway, which plays a significant role in the immune system's response to cancer. This makes it potentially useful for patients who cannot tolerate traditional platinum-based chemotherapy, offering a different mechanism of action by enhancing the body's immune response to fight cancer cells. ^{2 3 4 9 10}

What is the purpose of this trial?

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.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

1. England 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. [2022]

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

Carboplatin, methotrexate, and vinblastine in patients with bladder cancer who were ineligible for cisplatin-based chemotherapy. [2019]

3. Czech Republic pubmed.ncbi.nlm.nih.gov

[Immunotherapy for Bladder Cancer]. [2019]

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

Neoadjuvant Dose Dense MVAC versus Gemcitabine and Cisplatin in Patients with cT3-4aN0M0 Bladder Cancer Treated with Radical Cystectomy. [2022]

5. Spain pubmed.ncbi.nlm.nih.gov

[Preliminary results of a phase II randomized controlled trial comparing M-VAC and M-CAVI in patients with bladder cancer (T2-4 N0-1 M0)]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Which place for avelumab in the management of urothelial carcinoma? [2020]

7. Germany pubmed.ncbi.nlm.nih.gov

[First-line treatment of metastatic urothelial carcinoma : Update immuno-oncology]. [2020]

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

Bladder cancer. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Intra-arterial administration of methotrexate, adriamycin, and cisplatin as neoadjuvant chemotherapy for bladder cancer. [2019]

10. France pubmed.ncbi.nlm.nih.gov

[Metastases from urethelial carcinoma: role of chemotherapy]. [2022]