Gemcitabine + Cisplatin for Bladder Cancer

Recruiting at 366 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

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well gemcitabine hydrochloride and cisplatin work in treating participants with invasive bladder urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin, 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.

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.

What data supports the effectiveness of the drug Gemcitabine + Cisplatin for Bladder Cancer?

Research shows that the combination of Gemcitabine and Cisplatin is as effective as the previous standard treatment (MVAC) for advanced bladder cancer, with similar response rates and survival times, but with fewer severe side effects, making it a preferred option. ^{1 2 3 4 5}

What safety information is available for the combination of Gemcitabine and Cisplatin in treating bladder cancer?

The combination of Gemcitabine and Cisplatin has shown moderate toxicity in bladder cancer patients. Common side effects include nausea, vomiting, and effects on the kidneys (nephrotoxicity). Other potential side effects are myelosuppression (a decrease in bone marrow activity), hearing issues, and gastrointestinal problems. ^{6 7 8 9 10}

How is the drug combination of Gemcitabine and Cisplatin unique for treating bladder cancer?

The combination of Gemcitabine and Cisplatin is unique for treating bladder cancer because it offers a favorable balance of effectiveness and moderate side effects compared to the traditional M-VAC regimen, making it a preferred option, especially for elderly patients or those with kidney issues. ^{3 4 5 6 11}

Research Team

Gopa Iyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

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

My surgeon has approved me for major bladder surgery.

My bladder tumor is no larger than 5 cm, as confirmed by a bladder examination.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

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

The effect of platinum analogues and combination chemotherapy on murine bladder cancer. [2013]

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

Gemcitabine in advanced bladder cancer. [2022]

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

Gemcitabine/carboplatin in advanced urothelial cancer. [2022]

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

Tolerability of Gemcitabine Plus Cisplatin for Treatment of Urothelial Cancer in the Elderly Population. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Overview of gemcitabine triplets in metastatic bladder cancer. [2022]

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

Gemcitabine in the treatment of bladder cancer. [2022]

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

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022]

8. Japan pubmed.ncbi.nlm.nih.gov

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

9. Japan pubmed.ncbi.nlm.nih.gov

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

10. Australia pubmed.ncbi.nlm.nih.gov

Sequential therapy with gemcitabine and Carboplatin followed by Paclitaxel as first line treatment for advanced urothelial cancer. [2021]

11. Italy 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. [2022]