Celecoxib + Chemotherapy for Bladder Cancer

(BLAST Trial)

No longer recruiting at 1 trial location

Overseen By Aihua Edward Yen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must be taking: Gemcitabine, Cisplatin

Must not be taking: NSAIDs, Aspirin

Disqualifiers: Heart failure, Bleeding history, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 22 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adding celecoxib, a common anti-inflammatory medication, to chemotherapy can alter the behavior of bladder cancer cells. Researchers will examine gene changes in tumor tissues to understand celecoxib's effects when combined with the chemotherapy drugs cisplatin and gemcitabine. This trial is best suited for individuals with a specific type of bladder cancer called urothelial carcinoma, who have tumors at least 10 mm in size or that cause kidney swelling. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking cancer research.

Will I have to stop taking my current medications?

The trial requires that you stop regular use of NSAIDs (non-steroidal anti-inflammatory drugs) more than twice a week and aspirin more than 325 mg at least three times a week. Low-dose aspirin up to 100 mg per day is allowed, and no washout period is needed if you stop the higher doses.

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

Studies have shown that adding celecoxib to chemotherapy is generally well-tolerated. Research involving patients who took celecoxib with gemcitabine and cisplatin found this combination safe for most individuals. Another study reported that 28 patients aged 65 and older with bladder cancer tolerated the treatment well, with no major safety concerns. Although celecoxib did not significantly improve one-year survival rates when added to standard chemotherapy, it did not increase serious side effects either. This suggests the treatment is safe, even if its effectiveness varies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about combining Celecoxib with Gemcitabine and Cisplatin for bladder cancer because it offers a new approach to treatment. Unlike traditional chemotherapy that focuses solely on attacking cancer cells, Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that may enhance the effectiveness of chemotherapy by reducing inflammation, which is often linked to cancer growth. This dual-action approach—combining standard chemotherapy with an anti-inflammatory agent—could potentially improve outcomes by making cancer cells more susceptible to treatment, offering hope for better results compared to standard chemotherapy alone.

What evidence suggests that this trial's treatments could be effective for bladder cancer?

Research has shown that adding celecoxib to chemotherapy might enhance treatment effectiveness for bladder cancer. In this trial, participants will receive a combination of gemcitabine, cisplatin, and celecoxib, which previous studies with 28 patients with urothelial cancer found to be well-tolerated. The current trial tests whether this combination can better shrink tumors before surgery. Although some larger studies have shown limited benefits of celecoxib in cancer treatment, researchers hope this specific combination could yield better results for bladder cancer patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Aihua Edward Yen, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with localized, muscle-invasive bladder cancer who haven't had systemic chemotherapy. They need recent scans and tests showing good organ function, no severe neuropathy or uncontrolled illnesses, not pregnant/nursing, and can't be regularly using NSAIDs or have a history of significant bleeding or heart issues.

Inclusion Criteria

I can take care of myself and am up and about more than 50% of my waking hours.

Your blood tests must show: i. a certain amount of white blood cells, ii. a certain level of hemoglobin, and iii. a certain number of platelets.

My tumor is invasive, measures at least 10mm, or causes kidney swelling.

Exclusion Criteria

I haven't had serious bleeding issues in the last 6 months.

You cannot have asthma that is sensitive to aspirin.

I haven't had a stroke, heart attack, or severe angina in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive neoadjuvant chemotherapy with Celecoxib, Gemcitabine, and Cisplatin

22 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Celecoxib
• Cisplatin
• Gemcitabine

Trial Overview

The study is testing the effects of adding Celecoxib to standard chemotherapy (Cisplatin and Gemcitabine) on bladder cancer tissue. Researchers will compare gene expression in tumor samples taken before and after treatment to see how Celecoxib affects the cells.

How Is the Trial Designed?

Group I: Celecoxib plus Gemcitabine/Cisplatin chemo Experimental Treatment 3 Interventions

Celecoxib plus Gemcitabine/Cisplatin neoadjuvant chemotherapy

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?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

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 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]

Bladder cancer, often linked to environmental and lifestyle factors, shows promising outcomes with early intervention; 87% of early-stage patients can achieve 10-year survival after appropriate treatment, although many still require radical cystectomy.

Recent studies suggest that the gemcitabine and cisplatin regimen is as effective as traditional chemotherapy with less toxicity, making it the new standard for advanced bladder cancer treatment in ongoing phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bladder cancer. Patton, SE., Hall, MC., Ozen, H.[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]

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Celecoxib + Chemotherapy for Bladder Cancer (BLAST Trial)

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Giving celecoxib, gemcitabine hydrochloride, and cisplatin before surgery may work better in treating participants with bladder cancer.

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This review aims to present the current evidence for potentiating the efficacy of chemotherapy in bladder cancer.

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Compared to conventional chemotherapy alone, 1-year OS and 1-year PFS rates were not significantly improved with celecoxib adjuvant therapy (OS: ...