Celecoxib + Chemotherapy for Bladder Cancer

(BLAST Trial)

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

15 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to compare patient tumor tissue before and after treatment with chemotherapy plus celecoxib. Investigators will look at gene expression, to see what effect celecoxib may have on tumor cells.

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.

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

Research shows that the combination of Gemcitabine and Cisplatin is effective and less toxic than other regimens for advanced bladder cancer. Cisplatin-based chemotherapy is a standard treatment for muscle-invasive bladder cancer, improving survival rates. ^{1 2 3 4 5}

Is the combination of Celecoxib and chemotherapy safe for treating bladder cancer?

Cisplatin, a chemotherapy drug often used in bladder cancer treatment, can cause side effects like nausea, vomiting, and kidney problems. In some studies, severe blood-related side effects and kidney failure were noted, especially in patients with existing kidney issues. Gemcitabine, another chemotherapy drug, is generally considered safe but can also cause side effects like low blood counts and fatigue. ^{4 6 7 8 9}

What makes the drug combination of Celecoxib, Cisplatin, and Gemcitabine unique for treating bladder cancer?

This drug combination is unique because it includes Celecoxib, a COX-2 inhibitor, which may enhance the effects of chemotherapy drugs like Cisplatin and Gemcitabine by inhibiting tumor growth and reducing recurrence, offering a novel approach compared to standard treatments that typically rely on direct chemotherapy or immunotherapy alone. ^{10 11 12 13 14}

Research Team

Aihua Edward Yen, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

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

Bladder cancer. [2022]

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

A Single-arm Phase II Trial of Neoadjuvant Cabazitaxel and Cisplatin Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

State-of-the-art management of metastatic disease at initial presentation or recurrence. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

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

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

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

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

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

7. Japan pubmed.ncbi.nlm.nih.gov

[Antitumor effect of combined use of purified human natural tumor necrosis factor (N-TNF) and cis-diamminedichoroplatinum (II) (cisplatin) on the implanted bladder carcinoma (MBT-2) in mice]. [2019]

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

Boxing bladder cancer with COX-2-specific inhibition. [2021]

11. Greece pubmed.ncbi.nlm.nih.gov

Cyclin-mediated G1 arrest by celecoxib differs in low-versus high-grade bladder cancer. [2021]

12. England pubmed.ncbi.nlm.nih.gov

Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination. [2021]

13. Germany pubmed.ncbi.nlm.nih.gov

Cisplatin versus cisplatin combined with piroxicam in a canine model of human invasive urinary bladder cancer. [2013]

14. England pubmed.ncbi.nlm.nih.gov

Celecoxib for the prevention of nonmuscle invasive bladder cancer: results from a matched control study. [2020]