Gemcitabine + Cisplatin for Bladder Cancer

Recruiting in Palo Alto (17 mi)

+366 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Alliance for Clinical Trials in Oncology

Must not be taking: Antiretrovirals

Disqualifiers: HIV/AIDS, Heart disease, Neuropathy, others

No Placebo Group

Prior Safety Data

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.

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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.

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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.

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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)

Trial 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

Participant Groups

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.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Trinity Regional Medical Center Fort Dodge, IA

Northshore Oncology Associates-Covington Covington, LA

Michigan Healthcare Professionals Pontiac Pontiac, MI

Rhode Island Hospital Providence, RI

More Trial Locations

Who Is Running the Clinical Trial?

Alliance for Clinical Trials in Oncology Lead Sponsor

National Cancer Institute (NCI) Collaborator

References

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

The effect of platinum analogues and combination chemotherapy on murine bladder cancer. [2013] Cis-diamminedichloroplatinum II currently is the most effective chemotherapeutic agent in advanced bladder cancer. However, most of the objective responses are partial and/or of limited duration (average 6 months). In an effort to identify a more effective compound with less toxicity platinum analogues have been synthesized. Since results in the carcinogen-induced murine bladder cancer model have correlated with activity of drugs in man this model was used to evaluate 4 of these analogues. Although not as effective as the parent compound, cis-diamminedichloroplatinum, they exhibited significant antitumor activity in the poorly differentiated transplanted tumor. However, they were not able to reduce the incidence or size of primary tumors. Another approach to enhance tumor cell kill is combination chemotherapy. The addition of cyclophosphamide or cyclophosphamide and doxorubicin hydrochloride to cis-diamminedichloroplatinum produced a greater tumor inhibition than cis-diamminedichloroplatinum alone in experiments with the transplanted and the primary tumor models. It is hoped that these studies will continue to provide background information for the design of disease oriented phase I and II clinical trials.

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

Gemcitabine in advanced bladder cancer. [2022] The methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) regimen has been considered standard therapy for advanced bladder cancer. However, the toxicity of this regimen motivated the development of safer and/or more effective therapy. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) is a promising new agent with activity in advanced disease. Early phase studies yielded response rates of 23% to 29% with single-agent treatment and 41% to 57% with the combination of gemcitabine/cisplatin (GC). In a randomized phase III trial involving 405 randomized patients with locally advanced or metastatic bladder cancer, data comparing gemcitabine at 1,000 mg/m(2) on days 1, 8, and 15 plus cisplatin at 70 mg/m(2) on day 2 every 28 days with standard MVAC demonstrated that the two regimens were associated with comparable response rates, time to disease progression, and overall survival. The GC regimen was associated with superior safety and tolerability, including reduced frequencies of grade 3/4 mucositis (1% v 22%), neutropenic fever (2% v 14%), and neutropenic sepsis (1% v 12%). These findings suggested that on the basis of superior risk to benefit ratio, the GC regimen should be favored as standard treatment in advanced bladder cancer. Other promising combinations include gemcitabine/cisplatin/paclitaxel, and a phase III trial comparing this triple-agent combination with the GC regimen in advanced bladder cancer patients has been initiated. Semin Oncol 28 (suppl 7):11-14.

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

Gemcitabine/carboplatin in advanced urothelial cancer. [2022] Transitional cell carcinoma of the urothelium is a highly chemosensitive tumor. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. As shown in a recent phase III trial, the new gold standard should be considered gemcitabine/cisplatin, although toxicity remains important. Bladder cancer is a common tumor in our population (Spain), usually affecting elderly patients with comorbid diseases and renal impairment. Thus, most of these patients may not benefit from cisplatin-based regimens. The development of new combinations for treating such patients is, therefore, of vital importance. The identification of new active agents against transitional cell carcinoma, such as taxanes and gemcitabine, is promising. We believe that the combination of gemcitabine plus carboplatin could also be useful in this subset of patients. On this basis, we treated bladder cancer patients in two trials using gemcitabine 1,000 mg/m(2) on days 1 and 8, and carboplatin (area under the curve 5) on day 1, every 21 days. The overall response rate for evaluable patients with and without renal impairment was 60%, with a 95% confidence interval of 40% to 72%. The potential clinical benefit of this new doublet in the treatment of transitional cell carcinoma warrants testing in future phase III studies. Semin Oncol 28 (suppl 10):19-24.

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

Tolerability of Gemcitabine Plus Cisplatin for Treatment of Urothelial Cancer in the Elderly Population. [2022] Gemcitabine plus cisplatin is the standard of care for metastatic urothelial cancer and is frequently used in the neoadjuvant and adjuvant setting as well. However, the optimal dose and schedule for patients aged ≥ 65 years is not clear.

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

Overview of gemcitabine triplets in metastatic bladder cancer. [2022] For more than a decade the MVAC regimen has been gold standard chemotherapy in bladder cancer, albeit that the toxicity associated with this therapy hampered its use in many of the typical elderly patients with metastatic disease. New active agents have been identified, combinations of these new agents with platinum compounds (doublets) followed, and results have become available of a phase III randomized trial of the gemcitabine and cisplatin doublet versus MVAC, that has revealed an efficacy-toxicity profile in favor of the gemcitabine-cisplatin regimen. During the conduct of this study, investigators in Spain and in the United States have incorporated both gemcitabine and paclitaxel in either cisplatin- or carboplatin based triplet regimens that, albeit thus far only in phase II studies, have indicated notable activity and favorable median survival figures, particularly in patients with visceral disease. A randomized study of the paclitaxel-cisplatin-gemcitabine triplet versus gemcitabine-cisplatin is ongoing.

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

Gemcitabine in the treatment of bladder cancer. [2022] New agents are available for the treatment of metastatic transitional cell carcinoma of the bladder. In the US, the combination of methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) remains the standard chemotherapy regimen for advanced bladder cancer. Gemcitabine (2',2'-difluorodeoxycytidine [dFdC]) is a relatively new agent with a favourable toxicity profile that has demonstrated activity against a number of solid tumours in both preclinical and clinical studies. Single-agent gemcitabine has shown activity in bladder cancer in both pretreated and chemotherapy-naïve patients. The combination of gemcitabine plus cisplatin is a regimen with significant activity and moderate toxicity in bladder cancer patients. A randomised trial of gemcitabine plus cisplatin versus M-VAC has completed accrual but has not yet been reported. New combination studies of gemcitabine with other chemotherapy agents, including the taxanes, are ongoing.

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

Cis-diamminedichloroplatinum activity in bidimensionally measurable metastatic lesions of bladder carcinoma. [2022] Cis-diamminedichloroplatinum (CDDP) was administered i.v., at the dosage of 20 mg/m2 for 5 consecutive days and recycled every 3 weeks, to 11 patients with bidimensionally measurable metastatic lesions from bladder cancer previously untreated with antineoplastic drugs. Eight patients (6 men and 2 women) were evaluated for clinical response and 9 for toxicity. No complete regression was observed, and partial regression was obtained only in 3 patients (37.5%). Severe leukopenia and thrombocytopenia occurred only occasionally; moderate nausea and vomiting were observed in 5 cases. Nephrotoxicity was noted in 4 of the 9 patients evaluable for toxicity, and 2 of them, with ureteral obstruction, died of renal failure.

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

[Phase II study on cis-diamminedichloroplatinum (II) by a collaborative study]. [2013] Phase II study of cis-diaminedichloroplatinum(II) (CIS-DDP) administered intravenously was performed in 77 patients with urologic malignancies for the evaluation of clinical responses and adverse effects. The eligibility of the patients and evaluation of response were carried out according to the general criteria proposed by Drs. Koyama and Saito. Out of 85 patients, entered in this phase II study, 77 patients were considered evaluable. Complete responses were seen in 4 patients, 3 testicular tumor and 1 bladder cancer. Partial response were obtained in 24 patients; 10 bladder cancer, 8 testicular tumor, 5 prostatic cancer, and 1 renal cell carcinoma. Overall response rates were 73.3% in testicular tumor, 50.0% in bladder tumor, 20.8% in prostatic cancer, and 7.7% in renal cell carcinoma. Incidences of toxicities were noted in the gastrointestinal tract. Nausea, vomiting, anorexia, abdominal pain, and diarrhea were observed in 78.5% of the patients treated with CIS-DDP. Myelosuppression, lassitude, renal and hearing dysfunction were other prominent adverse effects.

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

[Phase II study of cis-diamminedichloroplatinum (II) in genitourinary cancer]. [2013] One hundred and twelve patients with evaluable genitourinary tumors were treated with cis-diamminedichloroplatinum (II) as a single agent under multi-institutional clinical trials. Most patients had extensive prior therapy. Of 30 patients with testicular tumors, 5 complete responses (16.7%) and 15 partial responses (50.0%), of 29 patients with bladder carcinoma, 2 CR (6.9%) and 7 PR (24.1%), of 34 patients with prostatic carcinoma, 6 PR (17.6%), and of 10 patients with pelvis and ureter carcinoma, 1 CR and 3 PR were obtained respectively. No responder was seen in eight patients with renal cell carcinoma and in one with urethral carcinoma. Adverse reactions were similar to those already reported including gastrointestinal reactions, nephrotoxicity and myelosuppression. Ototoxicity, peripheral neuropathies and transient elevation of GOT-GPT levels were occasionally encountered. Cis-diamminedichloroplatinum (II) appears to be highly active as a single agent in the treatment of advanced genitourinary tumors.

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] Gemcitabine and platinum-based compounds represent the new standard combination therapy for bladder cancer. In this study, we evaluate the efficacy and safety of gemcitabine and carboplatin followed sequentially by paclitaxel in 27 patients with advanced transitional cell carcinoma.

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] Cisplatin-based combination chemotherapy is the mainstay of treatment for advanced bladder cancer. However, full doses of cisplatin cannot be delivered in patients with impaired renal function. Our aim was to prove the feasibility of a gemcitabine and low-dose cisplatin regimen, delivered every two weeks in patients with impaired renal function.