Gemcitabine + Cisplatin for Bladder Cancer

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a chemotherapy combination of Gemcitabine and Cisplatin can shrink kidney cancer tumors before surgery. The focus is on high-grade urothelial carcinoma, a type of bladder cancer that affects the kidneys. Suitable candidates for this trial include those diagnosed with this specific cancer type, who are candidates for surgery, and are experiencing related symptoms or complications. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that using Gemcitabine and Cisplatin together is a common treatment for bladder cancer. Studies indicate that most patients tolerate this combination well. Compared to other treatments, it tends to be safer and causes fewer serious side effects.

In one study, patients taking Gemcitabine and Cisplatin experienced fewer severe side effects than those on another treatment called M-VAC, making it generally easier on the patients. While all treatments can have side effects, evidence suggests that Gemcitabine and Cisplatin are relatively safe for most people.

For those considering a trial with these medications, research supports their use as a less harmful option compared to some other chemotherapy treatments. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bladder cancer?

The combination of Gemcitabine and Cisplatin is unique because it offers a powerful one-two punch against bladder cancer by using both drugs together as neoadjuvant chemotherapy. While standard treatments often rely on surgery followed by chemotherapy, this combination is given before surgery to potentially shrink tumors, making them easier to remove and improving surgical outcomes. Researchers are excited because this approach might enhance the effectiveness of surgery and reduce the risk of cancer returning, offering a promising new avenue for treating high-grade urothelial carcinoma.

What evidence suggests that Gemcitabine and Cisplatin might be an effective treatment for bladder cancer?

Research has shown that using gemcitabine and cisplatin together effectively treats bladder cancer. Studies have found that this combination can shrink tumors and reduce symptoms in patients. In some cases, up to 70% of patients respond well to this treatment. Participants in this trial will receive the combination of gemcitabine and cisplatin. Compared to other treatments, patients receiving gemcitabine and cisplatin have similar survival rates to those on more toxic options. This combination is often chosen because it works well and is generally easier on the body than other chemotherapy treatments. ^{2 3 4 5 6}

Who Is on the Research Team?

Jonathan Coleman, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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

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.

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.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

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]

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. europeanurology.com europeanurology.com/article/S0302-2838(06)01589-2/pdf

Gemcitabine plus Cisplatin versus ... In particular, in metastatic urothelial cancer, single-agent gemcitabine has yielded response rates ranging from 23% to 29%, with complete response. (CR) rates ...

3. cancernetwork.com cancernetwork.com/view/gemcitabinecisplatin-said-offer-less-toxic-alternative-mvac-bladder-cance

Gemcitabine/Cisplatin Said to Offer Less Toxic Alternative ... After a median follow-up of 19 months, overall survival was 13.8 months in the gemcitabine/cisplatin arm and 14.8 months in the MVAC arm. There were 274 deaths.

4. chemoexperts.com chemoexperts.com/gemcitabine-gemzar-cisplatin-bladder-cancer.html

Gemcitabine (Gemzar®) + Cisplatin - Bladder Cancer Cisplatin plus gemcitabine is given to shrink bladder tumors and decrease symptoms from bladder cancer. It can be given either after surgery to ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02202772

Intravesical Cabazitaxel, Gemcitabine, and Cisplatin (CGC ... These drugs have shown some potential improvement for a small number of patients Given the synergy of systemic chemotherapy, it is believed that a multidrug ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8462587/

Randomized Phase III Trial of Gemcitabine and Cisplatin ... The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis ...