Gemcitabine + Cisplatin for Bladder Cancer

Recruiting at 384 trial locations

Overseen By Gopa Iyer, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Antiretrovirals

Disqualifiers: HIV/AIDS, Heart disease, Neuropathy, 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: 12 weeks

271 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of two chemotherapy drugs, gemcitabine and cisplatin, in treating bladder cancer. The goal is to determine if these drugs can halt cancer growth by killing tumor cells or preventing their spread. Participants will be divided into two groups: one group will attempt to preserve the bladder, while the other may undergo surgery or additional treatment. Individuals with invasive bladder cancer who have not received certain cancer treatments before and have a single tumor 5 cm or smaller might be suitable candidates. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are HIV-positive and on antiretroviral therapy, you are not eligible to participate due to potential interactions with the trial drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of gemcitabine and cisplatin is generally well-tolerated. Studies have found this treatment to be both safe and effective. In one study, patients who received these drugs responded well and did not experience severe side effects. Another study reported similar positive results, with patients handling the treatment well.

In summary, current research suggests that using gemcitabine and cisplatin together is safe, and most patients tolerate the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a personalized approach to bladder cancer therapy. Unlike standard treatments, which often involve radical cystectomy (surgical removal of the bladder), this trial incorporates a bladder-sparing approach for patients with specific genetic profiles, potentially preserving quality of life. Both treatments combine gemcitabine and cisplatin, but one arm allows for bladder preservation in patients with DDR gene alterations and lower-stage disease. This tailored strategy not only targets the cancer more precisely but also aligns with the growing trend of using genetic information to guide treatment decisions.

What evidence suggests that gemcitabine and cisplatin might be an effective treatment for bladder cancer?

Studies have shown that using gemcitabine and cisplatin together effectively treats bladder cancer. Earlier research indicated that patients with advanced bladder cancer had response rates between 40% and 70% after receiving this treatment, with many experiencing tumor shrinkage or halted growth. This trial will evaluate two different approaches using this combination. In one arm, participants will receive gemcitabine and cisplatin with a bladder-sparing approach. In the other arm, participants will receive the same combination followed by radical cystectomy or chemoradiotherapy. This combination has led to positive results in tumor response and overall survival, and patients have generally tolerated gemcitabine and cisplatin well. This evidence suggests that the treatment is promising for people with invasive bladder cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Gopa Iyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with muscle-invasive bladder urothelial cancer who are suitable for radical cystectomy, have not had systemic chemotherapy in the past 5 years, and no prior anti-PD-1 or anti PD-L1 therapies. They should not be pregnant or nursing, must have good organ function and performance status (able to carry out daily activities), and cannot have a history of certain heart conditions or other serious illnesses.

Inclusion Criteria

Total bilirubin =< 1.5 x upper limit of normal (ULN)

AST/ALT =< 2.5 x ULN

Alkaline phosphatase =< 2.5 x ULN

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive gemcitabine hydrochloride and cisplatin chemotherapy every 14 days for up to 6 courses

12 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Extension/Long-term follow-up

Participants are followed up for recurrence-free and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cisplatin
• Gemcitabine Hydrochloride

Trial Overview The trial tests how well gemcitabine hydrochloride and cisplatin treat invasive bladder urothelial cancer without surgery. It's a phase II study where these chemotherapy drugs aim to stop tumor growth by killing cells or preventing them from dividing/spreading.

How Is the Trial Designed?

Group I: Arm II (gemcitabine, cisplatin, cystectomy, chemoradiotherapy) Experimental Treatment 5 Interventions

Participants receive gemcitabine hydrochloride IV over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim SC on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants with DDR gene alteration and disease stage \>= cT1 or participants without DDR gene alteration undergo radical cystectomy or chemoradiotherapy.

Group II: Arm I (gemcitabine, cisplatin, bladder sparing) Experimental Treatment 4 Interventions

Participants receive gemcitabine hydrochloride IV over 30 minutes on day 1, cisplatin IV on days 1 and 2, and pegfilgrastim SC on day 3. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unaccepted toxicity. Participants with DDR gene alteration and disease stage \< cT1 undergo bladder sparing.

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

Approved in European Union as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in United States as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Canada as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Approved in Japan as Platinol for:

• Testicular cancer
• Ovarian cancer
• Cervical cancer
• Bladder cancer
• Head and neck cancer
• Esophageal cancer
• Lung cancer
• Mesothelioma
• Brain tumors
• Neuroblastoma

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology

Lead Sponsor

Trials

521

Recruited

224,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The gemcitabine and cisplatin doublet regimen has shown a better efficacy-toxicity profile compared to the traditional MVAC chemotherapy for bladder cancer, making it a more suitable option for elderly patients with metastatic disease.

Ongoing phase II studies of triplet regimens combining gemcitabine, paclitaxel, and either cisplatin or carboplatin have demonstrated promising activity and improved median survival, particularly in patients with visceral disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. de Wit, R., Bellmunt, J.[2022]

In a phase III trial with 405 patients, the gemcitabine/cisplatin (GC) regimen showed comparable effectiveness to the standard MVAC regimen for advanced bladder cancer, with similar response rates and overall survival.

The GC regimen demonstrated significantly better safety and tolerability, with much lower rates of severe side effects like mucositis and neutropenic fever, suggesting it should be preferred as the standard treatment for advanced bladder cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine in advanced bladder cancer. von der Maase, H.[2022]

Cis-diamminedichloroplatinum II is currently the most effective treatment for advanced bladder cancer, but responses are often only partial and last about 6 months.

New platinum analogues showed significant antitumor activity in a murine bladder cancer model, and combining cis-diamminedichloroplatinum with cyclophosphamide or doxorubicin resulted in greater tumor inhibition than using cis-diamminedichloroplatinum alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of platinum analogues and combination chemotherapy on murine bladder cancer. Soloway, MS., Cox, CE.[2013]

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 carboplatin shows a promising overall response rate of 60% in treating transitional cell carcinoma of the bladder, making it a potential alternative for patients who cannot tolerate cisplatin due to renal impairment or other comorbidities.

Given the high chemosensitivity of transitional cell carcinoma, this new treatment combination warrants further investigation in future phase III trials to confirm its efficacy and safety in a broader patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gemcitabine/carboplatin in advanced urothelial cancer. Carles, J., Nogué, M.[2022]

In a Phase II study involving 77 patients with urologic malignancies, cis-diaminedichloroplatinum(II) (CIS-DDP) demonstrated significant efficacy, with overall response rates of 73.3% for testicular tumors and 50.0% for bladder tumors, indicating its potential as an effective treatment option.

However, the treatment was associated with considerable adverse effects, including gastrointestinal issues in 78.5% of patients, as well as myelosuppression and renal dysfunction, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study on cis-diamminedichloroplatinum (II) by a collaborative study]. [2013]

In a study of 28 patients aged 65 and older with urothelial cancer, the combination of gemcitabine and cisplatin was found to be reasonably well-tolerated, with 57.1% receiving it in the neoadjuvant setting.

The study suggests that a lower dose of gemcitabine (1000 mg/m²) is better tolerated than the standard higher dose (1250 mg/m²), as higher doses led to more hematologic toxicity and treatment delays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability of Gemcitabine Plus Cisplatin for Treatment of Urothelial Cancer in the Elderly Population. Jan, AS., Dolan, DE., Lombardi, K., et al.[2022]

A study involving 17 patients with advanced bladder cancer and impaired renal function demonstrated that a regimen of gemcitabine and low-dose cisplatin is safe, with no patients experiencing renal toxicity or worsening of kidney function.

The treatment resulted in a 53.3% overall response rate, including one complete response and seven partial responses, indicating that this low-dose combination is effective and comparable to standard dosing regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasiblity study of gemcitabine and cisplatin administered every two weeks in patients with advanced urothelial tumors and impaired renal function. Carles, J., Suárez, C., Mesía, C., et al.[2022]

In a study of 11 patients with untreated metastatic bladder cancer, cis-diamminedichloroplatinum (CDDP) showed a partial response in 37.5% of patients, indicating some efficacy in this difficult-to-treat population.

While CDDP was generally tolerated, it caused moderate nausea and vomiting in some patients, and nephrotoxicity was a significant concern, leading to renal failure in 2 patients with ureteral obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. De Lena, M., Lorusso, V., Iacobellis, U., et al.[2022]

Cis-diamminedichloroplatinum (II) demonstrated significant efficacy as a single-agent treatment for advanced genitourinary tumors, achieving complete responses in 16.7% of testicular cancer patients and partial responses in 50% of the same group, based on a study of 112 patients with various genitourinary tumors.

The treatment was associated with common adverse reactions such as gastrointestinal issues, nephrotoxicity, and myelosuppression, but also included occasional ototoxicity and peripheral neuropathies, indicating a need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Phase II study of cis-diamminedichloroplatinum (II) in genitourinary cancer]. [2013]

In a phase II study involving 27 patients with advanced transitional cell carcinoma, the sequential treatment of gemcitabine and carboplatin followed by paclitaxel resulted in an objective response rate of 40.7%, with one complete response and ten partial responses.

The treatment was generally safe, with hematologic toxicities being the most common, but the study concluded that while this sequential approach appears safer than triplet therapy, it did not significantly improve patient outcomes, indicating a need for further research with larger groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. Kattan, JG., Boutros, CY., Farhat, FS., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2741662/

Efficacy of Combined Gemcitabine/Cisplatin Chemotherapy ... In the Phase III studies of MVAC therapy for patients with advanced urothelial TCC, the overall response rates were found to be 40~70% and median survival ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.4_suppl.589

Clinical outcomes with split-dose cisplatin-based regimens ... Background: Gemcitabine + cisplatin (GC) is one of the most effective and commonly used regimens in la/mUC. In GC, cisplatin is dosed at 70 ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2309863

Nivolumab plus Gemcitabine–Cisplatin in Advanced ... Combination therapy with nivolumab plus gemcitabine–cisplatin resulted in significantly better outcomes in patients with previously untreated advanced ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1078143925000353

Efficacy and safety of dose-dense gemcitabine ... Dose-dense gemcitabine and cisplatin showed a favorable pathological response and oncological outcome with good tolerability.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25872978/

Comparative effectiveness of gemcitabine plus cisplatin ... Patients who received neoadjuvant GC and MVAC achieved comparable pCR rates in the current analysis, providing evidence to support what has ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38994523/

Implications for Efficacy and Safety of Total Dose and ... A significantly higher complete response-rate was observed in the patient group treated with the more cisplatin-dose-intense 3-week schedule.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1558767324001472

Split-Dose Cisplatin in Patients With Locally Advanced or ... Split-dose GC had objective response rates (ORRs) of 39%-80%, median progression-free survival (PFS) of 3.5-9.9 months, and median overall survival (OS) of 8.5 ...

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa0908721

Cisplatin plus Gemcitabine versus Gemcitabine for Biliary ... The 6-month progression-free survival rate was 59.3% in the cisplatin–gemcitabine group and 42.5% in the gemcitabine-only group. Figure 2.