Gemcitabine + Docetaxel for Bladder Cancer

(GEMDOCE Trial)

Overseen By Max Kates, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Must not be taking: Chemotherapy, Immunotherapy

Disqualifiers: Muscle-invasive cancer, Upper tract cancer, Second malignancy, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, gemcitabine and docetaxel (a type of chemotherapy), to determine their safety and effectiveness for people with a specific type of bladder cancer that hasn't invaded the muscle layer. The study targets patients who haven't received a common treatment called BCG (a type of immunotherapy). Suitable candidates are those with intermediate or high-risk non-muscle invasive bladder cancer (cancer still in the bladder lining) who haven't experienced muscle-invasive or advanced cancer spread. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you have received anti-cancer therapy or radiotherapy recently, you must wait at least 4 weeks before starting the study drug.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that a combination of gemcitabine and docetaxel administered directly in the bladder has been tested in people with bladder cancer. These studies found that most participants tolerated the treatment well. While some experienced mild to moderate side effects, serious issues were rare.

For instance, some participants felt discomfort during treatment, but major problems were uncommon. This indicates that the treatment is generally safe, especially since it is now in a phase 2 trial, meaning it has already passed initial safety tests. It is important to consult a healthcare provider to understand personal risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for bladder cancer?

Researchers are excited about the Gemcitabine + Docetaxel treatment for bladder cancer because it uses a unique delivery method. Unlike traditional treatments that are often systemic, this combination is administered directly into the bladder through a Foley catheter. This intravesical approach allows the drugs to target cancer cells more directly, potentially reducing side effects and improving effectiveness. By clamping the catheter, the treatment is given time to work directly where it's needed, which could lead to better patient outcomes compared to standard chemotherapy methods.

What evidence suggests that this treatment might be an effective treatment for bladder cancer?

Research has shown that using a combination of gemcitabine and docetaxel directly in the bladder for treating non-muscle invasive bladder cancer (NMIBC) is very promising. In this trial, participants will receive intravesical gemcitabine/docetaxel treatment. Specifically, studies found that 97% of patients did not experience cancer progression over 24 months. This treatment also reduces the likelihood of cancer recurrence compared to other treatments like BCG therapy. Although some patients find it challenging to complete the entire treatment, many experience positive results. Overall, this combination is effective for those who have not yet tried BCG treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

Max Kates, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

This trial is for adults with early-stage bladder cancer that hasn't spread into the muscle. They should be in fairly good health, not pregnant or breastfeeding, and haven't had certain cancer treatments recently. People with more advanced cancer, another serious active cancer, or those who've used gemcitabine or docetaxel for other cancers can't join.

Inclusion Criteria

Subjects who give a written informed consent obtained according to local guidelines

I am post-menopausal or not pregnant.

I am able to care for myself and perform daily activities.

Exclusion Criteria

I have another cancer with a life expectancy of less than 12 months.

I received cancer treatment less than 4 weeks ago or am still experiencing side effects.

I had radiotherapy less than 4 weeks ago or still have side effects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an induction course of gemcitabine/docetaxel instillations once a week for six consecutive weeks

6 weeks

6 visits (in-person)

Maintenance

Monthly maintenance instillations of Gemcitabine/Docetaxel if initial efficacy is seen

Up to 24 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Gemcitabine

Trial Overview

The study tests a combination of two drugs, Gemcitabine and Docetaxel, given directly into the bladder to treat patients who have never received BCG therapy. It's an open-label phase 2 study which means everyone gets the treatment and researchers track its safety and effectiveness.

How Is the Trial Designed?

Group I: Intravesical Gemcitabine/Docetaxel Experimental Treatment 2 Interventions

Gemcitabine/Docetaxel induction is given intravesically in sequential order once a week for six consecutive weeks. One gram of gemcitabine in 50 ml of sterile water is slowly instilled into the bladder via a Foley catheter and the catheter is clamped for 60 minutes. The bladder is then drained and 40 mg of docetaxel in 50 ml of NSS is then slowly instilled via the Foley catheter into the bladder. The catheter is again clamped for 60 minutes before draining. If initial efficacy seen, patients will have monthly maintenance instillations of Gemcitabine/Docetaxel.

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?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

Published Research Related to This Trial

The combination of docetaxel and gemcitabine offers a promising second-line treatment option for patients with non-muscle-invasive bladder cancer that does not respond to bacillus Calmette-Guérin therapy.

Both drugs are well tolerated as individual treatments and have different mechanisms of action, making their combination a potentially effective and affordable standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential Gemcitabine plus Docetaxel Is the Standard Second-line Intravesical Therapy for BCG-unresponsive Non-muscle-invasive bladder cancer: Pro. Roumiguié, M., Black, PC.[2022]

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]

The combination of gemcitabine and docetaxel showed a 51.6% overall response rate in 31 patients with advanced urothelial carcinoma, indicating significant efficacy as a first-line treatment.

The treatment was well tolerated, with manageable hematologic toxicities and no toxic deaths, suggesting it could be a safer alternative for patients with compromised renal function or cardiovascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine and docetaxel as first-line treatment for advanced urothelial carcinoma: a phase II study. Ardavanis, A., Tryfonopoulos, D., Alexopoulos, A., et al.[2022]

In a study of 35 patients with advanced transitional cell carcinoma (TCC), a combination of weekly docetaxel, gemcitabine, and cisplatin resulted in a high objective response rate of 65.6%, with 28.5% achieving a complete response.

The treatment was associated with moderate toxicity, including grade 3/4 neutropenia in 28.5% of patients, but no treatment-related deaths occurred, suggesting it is a safe and effective option for chemotherapy-naïve patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weekly chemotherapy with docetaxel, gemcitabine and cisplatin in advanced transitional cell urothelial cancer: a phase II trial. Pectasides, D., Glotsos, J., Bountouroglou, N., et al.[2022]

In a Phase II trial involving 29 patients with advanced urothelial carcinoma, the combination of gemcitabine and docetaxel showed an overall response rate of 17%, indicating it can be an effective second-line treatment option for this patient group.

The treatment was associated with moderate toxicity, primarily granulocytopenia, anorexia, and fatigue, highlighting the need for careful monitoring, especially due to reported thromboembolic symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of gemcitabine and docetaxel in patients with advanced carcinoma of the urothelium: a trial of the Eastern Cooperative Oncology Group. Dreicer, R., Manola, J., Schneider, DJ., 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]

In a study of 27 patients with unresectable metastatic or locally advanced transitional cell carcinoma, the combination of gemcitabine and docetaxel showed a 33.3% objective clinical response rate, with a median survival duration of 52 weeks.

The treatment was generally well tolerated, with neutropenia being the most common severe side effect, indicating that this combination therapy could be a viable option for patients who cannot receive cisplatin due to renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinoma. Gitlitz, BJ., Baker, C., Chapman, Y., 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]

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Sequential Intravesical Gemcitabine and Docetaxel for the ...

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4320-Bladder intravesical DOCEtaxel and gemcitabine

Milbar et al. validated these results in a similar population reporting disease-free survival (DFS) of 42% at 1 year and 24% at 2 years (median DFS 7 months).