Gemcitabine + Cisplatin for Bladder Cancer

Recruiting at 8 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Investigational drugs

Disqualifiers: Heart disease, Neuropathy, Hypertension, 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: 4

57 Participants Needed

Trial Summary

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 take other investigational drugs or be on another clinical trial that might affect the study's main outcome.

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

Research shows that the combination of Gemcitabine and Cisplatin is effective for treating bladder cancer, with a better balance of effectiveness and side effects compared to older treatments. It is considered the standard care for advanced bladder cancer, offering a survival advantage and being less toxic than some other chemotherapy options. ^{1 2 3 4 5}

What safety data exists for the combination of Gemcitabine and Cisplatin in treating bladder cancer?

Gemcitabine and Cisplatin have been used together for bladder cancer treatment, but they can cause side effects. Cisplatin may lead to nausea, vomiting, kidney problems, and blood cell issues, while Gemcitabine is generally well-tolerated but can also cause similar side effects. It's important to manage these side effects to avoid treatment delays. ^{6 7 8 9 10}

How does the drug Gemcitabine + Cisplatin differ from other treatments for bladder cancer?

Gemcitabine combined with Cisplatin is favored over the older MVAC regimen for advanced bladder cancer due to its better safety profile, with fewer severe side effects like mouth sores and infections. This combination is now considered a standard treatment because it offers similar effectiveness with improved tolerability, especially important for elderly patients who may not tolerate more toxic treatments. ^{1 2 3 7 11}

What is the purpose of this trial?

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin for four 21 day cycles for a total of 12 weeks can help shrink the tumor before undergoing surgery for kidney cancer.

Research Team

Jonathan Coleman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with high-grade upper tract transitional cell carcinoma who are fit for kidney surgery. They must have certain blood and organ function levels, not be pregnant or breastfeeding, use effective contraception, and have no recent major heart issues or surgeries. Prior systemic chemotherapy disqualifies them.

Inclusion Criteria

My cancer is a high-grade type in the upper urinary tract, confirmed by tests.

I am a suitable candidate for major kidney or ureter surgery, as determined by a specialist.

Required Initial Laboratory Values: Absolute neutrophil count ≥ 1500 cells/mm3, Platelets ≥ 100,000 cells/mm3, Hemoglobin ≥ 9.0g/dL, Bilirubin ≤ 1.2, Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution, Alkaline phosphatase ≤ 2.5 x ULN for the institution, Serum creatinine ≤ 1.3 mg/dL if male or ≤ 1.1 mg/dL if female OR calculated creatinine clearance ≥ 55 ml/min/1.73m^2, If female of childbearing potential, serum pregnancy test is negative, Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial.

Exclusion Criteria

I have a heart rhythm problem that is moderate to severe.

I do not have any serious ongoing health or mental health conditions.

Concomitant use of any other investigational drugs

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive Gemcitabine and Cisplatin for four 21-day cycles to shrink the tumor before surgery

12 weeks

4 visits (in-person, every 3 weeks)

Surgery

Participants undergo radical nephroureterectomy or distal ureterectomy

Follow-up

Participants are monitored for safety, effectiveness, and disease progression after treatment

3 years

Treatment Details

Interventions

• Cisplatin
• Gemcitabine

Trial Overview The study tests if Gemcitabine and Cisplatin chemotherapy given over four cycles (each lasting 21 days) can shrink kidney tumors before surgery. The treatment spans a total of 12 weeks.

Participant Groups

Group I: Gemcitabine and Cisplatin Experimental Treatment 1 Intervention

This is a Phase II Study of Gemcitabine and Cisplatin (GC) as neoadjuvant chemotherapy in patients with upper tract high-grade urothelial carcinoma who are candidates for radical nephroureterectomy or distal ureterectomy.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Hartford Hospital

Collaborator

Trials

140

Recruited

19,700+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Findings from Research

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 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 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 22 patients with muscle-invasive bladder cancer, neoadjuvant chemotherapy using gemcitabine plus cisplatin achieved downstaging rates of 50% to pT0 and 63.6% to <pT2, which is comparable to the rates achieved with methotrexate, vinblastine, doxorubicin, and cisplatin in a comparator group of 9 patients.

Gemcitabine plus cisplatin demonstrated a better safety profile, with significantly lower rates of non-hematologic toxicity compared to the traditional chemotherapy regimen, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant gemcitabine plus cisplatin for muscle-invasive bladder cancer. Kaneko, G., Kikuchi, E., Matsumoto, K., et al.[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]

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 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]

The sequential treatment of gemcitabine and cisplatin followed by docetaxel showed a promising objective response rate of 55.2% in 38 patients with advanced urothelial carcinoma, indicating its efficacy as a first-line therapy.

The treatment was generally well tolerated, with manageable side effects; although 27% experienced severe neutropenia during the GP regimen, there were no toxic deaths reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. Boukovinas, I., Androulakis, N., Vamvakas, L., et al.[2022]

Cisplatin is a key treatment for bladder cancer, but managing its side effects, like nausea and acute kidney injury, is crucial to maintain treatment effectiveness and avoid dose reductions.

An effective strategy for preventing cisplatin-associated nausea and vomiting involves a four-drug prophylactic regimen, while intensive hydration is essential for preventing acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of cisplatin-associated toxicities in bladder cancer patients. Desilets, A., Adam, JP., Soulières, D.[2021]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

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

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

Gemcitabine/carboplatin in advanced urothelial cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Neoadjuvant gemcitabine plus cisplatin for muscle-invasive bladder cancer. [2022]

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

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

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

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

7. Australia pubmed.ncbi.nlm.nih.gov

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

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

Sequential gemcitabine and cisplatin followed by docetaxel as first-line treatment of advanced urothelial carcinoma: a multicenter phase II study of the Hellenic Oncology Research Group. [2022]

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

Management of cisplatin-associated toxicities in bladder cancer patients. [2021]

10. Japan pubmed.ncbi.nlm.nih.gov

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

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

Gemcitabine in advanced bladder cancer. [2022]