In-home Chemotherapy for Bladder Cancer

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must be taking: Gemcitabine, Bacillus Calmette-Guerin

Must not be taking: Investigational agents

Disqualifiers: Active infection, Heart failure, others

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

Compensation: Varies

Number of Visits: 5

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase Ib/II trial compares the safety, tolerability and acceptability of intravesical chemotherapy given at home to in-clinic administration in patients with non-muscle invasive bladder cancer. Chemotherapy drugs, such as bacillus Calmette-Guerin (BCG), gemcitabine, docetaxel, and mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Standard of care chemotherapy for non-invasive bladder cancer is usually given directly into the bladder through a catheter (intravesical). This process requires numerous visits and can be disruptive to the lives of patients and caregivers. Bringing cancer care to the patients with in-home intravesical therapy may help reduce the disruption to daily lives. In-home intravesical chemotherapy may be safe and tolerable and may also be preferable to in-clinic administration in patients with non-muscle invasive bladder cancer.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you are receiving other treatments for bladder cancer that are not part of the eligible regimens.

What data supports the effectiveness of the drug combination including Docetaxel and Gemcitabine for bladder cancer?

Research shows that the combination of Gemcitabine and Docetaxel, when used intravesically (directly into the bladder), can effectively reduce tumor and metastatic burden in bladder cancer, suggesting it may be a promising treatment option. ^{1 2 3 4 5}

What safety data exists for in-home chemotherapy using gemcitabine and docetaxel for bladder cancer?

Studies have shown that the combination of gemcitabine and docetaxel is generally safe for treating nonmuscle-invasive bladder cancer, with research focusing on its use in patients who cannot use other treatments. While these studies primarily focus on hospital settings, they provide a basis for understanding the safety of these drugs in humans. ^{3 6 7 8 9}

What makes the in-home chemotherapy treatment for bladder cancer unique?

The in-home chemotherapy treatment for bladder cancer using Docetaxel, Gemcitabine, and Mitomycin is unique because it combines these newer agents, which have shown promising results in clinical trials, with the convenience of home administration, potentially reducing the need for hospital visits and improving patient comfort. ^{1 10 11 12 13}

Research Team

Timothy D. Lyon, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for patients with non-muscle invasive bladder cancer. It's designed to test if chemotherapy at home is as safe and tolerable as treatment in a clinic. Participants should be comfortable receiving treatments through a catheter into the bladder and completing questionnaires.

Inclusion Criteria

Residing within the area serviced by supplier network

Residence has Wi-Fi or cellular data network connection for virtual telehealth visits

Signed informed consent form by patient or the patient's legally authorized representative

Exclusion Criteria

Receiving any other investigational or standard of care agent not part of the eligible treatment regimens for non-muscle invasive bladder cancer

Current inpatient hospitalization excluding admission to the Advanced Care at Home program

Known allergy or previous intolerance to drug regimens

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive intravesical chemotherapy in the urology clinic and at home once weekly for up to 5 weeks

5 weeks

5 visits (in-home)

Maintenance

Patients receive in-home intravesical therapy once weekly for 3 weeks or once monthly for 3 months depending on the drug regimen

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Treatment Details

Interventions

• Docetaxel
• Gemcitabine
• Mitomycin

Trial Overview The INVITE trial compares at-home versus in-clinic intravesical chemotherapy using drugs like BCG, gemcitabine, docetaxel, and mitomycin C. The study aims to see if home treatment can reduce life disruption for patients while being safe.

Participant Groups

Group I: Treatment (BCG, gemcitabine, docetaxel, mitomycin) Experimental Treatment 7 Interventions

INDUCTION (PHASE IB COHORT AND PHASE II COHORT): Patients receive BCG intravesically over 1-2 hours, gemcitabine intravesically over 1-2 hours, gemcitabine intravesically over 1 hour followed by docetaxel intravesically over 1 hour or mitomycin C intravesically over 1-2 hours in the urology clinic. Treatment repeats once weekly in the home for up to 5 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE (PHASE II COHORT ONLY): Patients receive in-home BCG intravesically over 1-2 hours once weekly for 3 weeks, gemcitabine intravesically over 1-2 hours once monthly for 3 months, gemcitabine intravesically over 1 hour followed by docetaxel intravesically over 1 hour once monthly for 3 months or mitomycin C intravesically over 1-2 hours once monthly for 3 months in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo cystoscopy at end of study and receive access to CCBW home health visits throughout the study.

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

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Findings from Research

Current treatments for muscle-invasive bladder cancer, including radical cystectomy and chemotherapy, have a cure rate of only about 50%, with many patients developing metastases within two years.

New agents like taxanes (paclitaxel and docetaxel) and gemcitabine show promising results in preliminary phase II studies, suggesting they could enhance treatment outcomes when combined with existing chemotherapy regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The role of new drugs in the treatment of locally advanced urothelial tumors of the bladder]. Antoine, EC., Khayat, D.[2022]

In a study of 277 patients with muscle-invasive bladder cancer or locally advanced upper tract urothelial cancer, both high dose-intensity combination chemotherapy (HD MVAC) and gemcitabine plus cisplatin (GC) showed similar oncologic outcomes, with no significant differences in pathologic complete response rates or overall survival after 3 years.

However, HD MVAC was associated with a higher risk of febrile neutropenia compared to GC, indicating that while both treatments are effective, HD MVAC may pose additional safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes in patients with localized or locally advanced urothelial carcinoma treated with neoadjuvant chemotherapy involving gemcitabine-cisplatin and high dose-intensity MVAC. Lee, Y., Kim, YS., Hong, B., et al.[2022]

In a study of 59 patients with nonmuscle-invasive bladder cancer treated with intravesical gemcitabine/docetaxel (GEM/DOCE), the overall disease-free survival (DFS) was 49% at 1 year and 29% at 2 years, indicating that GEM/DOCE is a viable treatment option, especially for those who have failed previous therapies.

Patients who received monthly maintenance therapy after an initial complete response to GEM/DOCE had significantly better DFS rates (81% at 1 year) compared to those who were only observed (42% at 1 year), suggesting that maintenance therapy enhances long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer. Daniels, MJ., Barry, E., Milbar, N., et al.[2022]

Intravesical gemcitabine and docetaxel therapy shows promising efficacy for high-risk nonmuscle invasive bladder cancer, with 1-year and 2-year recurrence-free survival rates of 86% and 84% in BCG-naive patients, and 80%, 66%, and 51% in BCG-unresponsive patients at 6 months, 1 year, and 2 years, respectively.

The treatment is generally well tolerated, with only 2.3% of patients unable to complete induction therapy and 6.9% experiencing delays or dose reductions due to adverse events, suggesting it could be a viable alternative to BCG therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis. Kawada, T., Yanagisawa, T., Araki, M., et al.[2023]

In a randomized phase III trial involving 220 patients with inoperable or metastatic urothelial carcinoma, the MVAC regimen demonstrated superior response rates (54.2% vs. 37.4%) and longer median time to progression (9.4 months vs. 6.1 months) compared to the docetaxel and cisplatin (DC) combination.

While MVAC was more effective, it also resulted in higher rates of severe side effects, such as neutropenia and neutropenic sepsis, although the toxicity was lower than previously reported for MVAC without G-CSF support, suggesting that G-CSF makes MVAC a safer option for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. Bamias, A., Aravantinos, G., Deliveliotis, C., et al.[2018]

Gemcitabine, a newer chemotherapy agent, has shown promising activity against bladder cancer, both as a single agent and in combination with cisplatin, offering a favorable toxicity profile compared to traditional treatments.

The standard treatment for advanced bladder cancer in the US remains the M-VAC regimen, but ongoing trials are exploring the effectiveness of gemcitabine combined with other agents, which may lead to improved treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. Ryan, CW., Vogelzang, NJ.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

[The role of new drugs in the treatment of locally advanced urothelial tumors of the bladder]. [2022]

2. Germany pubmed.ncbi.nlm.nih.gov

Comparison of clinical outcomes in patients with localized or locally advanced urothelial carcinoma treated with neoadjuvant chemotherapy involving gemcitabine-cisplatin and high dose-intensity MVAC. [2022]

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

An evaluation of monthly maintenance therapy among patients receiving intravesical combination gemcitabine/docetaxel for nonmuscle-invasive bladder cancer. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

State-of-the-art management of metastatic disease at initial presentation or recurrence. [2022]

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

Preclinical analyses of intravesical chemotherapy for prevention of bladder cancer progression. [2022]

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

Sequential endoluminal gemcitabine and docetaxel for the treatment of clinically non-invasive high-grade upper tract urothelial carcinoma. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel as second-line chemotherapy in elderly patients with metastatic urothelial carcinoma: a retrospective analysis. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Intravesical gemcitabine versus mitomycin for non-muscle invasive bladder cancer: a systematic review and meta-analysis of randomized controlled trial. [2022]

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

Sequential intravesical gemcitabine and docetaxel therapy in patients with nonmuscle invasive bladder cancer: a systematic review and meta-analysis. [2023]

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

Docetaxel and cisplatin with granulocyte colony-stimulating factor (G-CSF) versus MVAC with G-CSF in advanced urothelial carcinoma: a multicenter, randomized, phase III study from the Hellenic Cooperative Oncology Group. [2018]

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

In vivo evaluation of mucoadhesive nanoparticulate docetaxel for intravesical treatment of non-muscle-invasive bladder cancer. [2018]

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

Gemcitabine and paclitaxel every 2 weeks in patients with previously untreated urothelial carcinoma. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Gemcitabine in the treatment of bladder cancer. [2022]