Celecoxib With Chemotherapy in Localized, Muscle-Invasive Bladder Cancer (BLAST)

Pilot Study of Celecoxib Combined With Gemcitabine and Cisplatin for Neoadjuvant Treatment of Localized, Muscle-Invasive Bladder Cancer

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Celecoxib; Drug: Gemcitabine; Drug: Cisplatin

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Aihua Edward Yen, MD; Phone Number: 713-798-3750; Email: ay044661@bcm.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77054
      • Harris Health System - Smith Clinic
    • Houston, Texas, United States, 77030
      • Baylor Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects or their legally authorized representative must be informed of the investigational nature of this study, and must sign and give written informed consent in accordance with institutional and federal guidelines.
• Patients must have histologically proven urothelial carcinoma of the bladder. Those with mixed histology, including a component of urothelial carcinoma, are eligible. Pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded.
• Patients must have Stage cT2-T4a N0 M0 disease. Clinical T stage is based on the TURBT sample, exam under anesthesia and cross-sectional imaging studies. Patients must undergo cystoscopy and TURBT as part of the staging procedure within 120 days prior to registration.

To exclude non-bulky/low-risk tumors, subjects must have documented muscle invasion with at least one of the following:

i. Disease measuring at least 10 mm on cross-sectional imaging. Bladder thickening on imaging, by itself, is not adequate.

ii. The presence of tumor-associated hydronephrosis.

• Patients must have staging scans with abdominal/pelvic CT or MRI scan, and CT scan or x-ray of the chest within 56 days prior to registration. If the alkaline phosphatase is > 1.5 x upper limit of normal (ULN), there is a presence of suspicious bone pain, or if there is other clinical suspicion of bone metastases, a whole body bone scan is required within 56 days prior to registration.
• Patients must have a Zubrod performance status of 0, 1 or 2.
• Patients must be 18 years of age or older.
• Patients must have adequate renal function as evidenced by calculated creatinine clearance ≥ 50 mL/min. The serum creatinine value used in the calculation must have been obtained within 28 days prior to registration.

• Patients must have adequate hepatic function (within 28 days prior to registration), defined as:

  i. Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 2.5 x ULN with Gilbert's disease); and ii. SGOT (AST) ≤ 2 x institutional ULN; and iii. SGPT (ALT) ≤ 2 x institutional ULN.

• Patients must have adequate hematologic function (within 28 days prior to registration), defined as:

  i. Absolute neutrophil count (ANC) ≥ 1,500/μL; and ii. Hemoglobin ≥ 9 g/dL; and iii. Platelets ≥ 100,000/μL.

• Patients must have tumor tissues from transurethral resection of the bladder tumor (TURBT) that is within 120 days of registration and available for submission. Tissue sample must be sufficient for IHC testing; that is,it must be sufficient tumor tissues for correlative science after pathologic diagnosis [i.e., enough tumor tissue to pass the staging criteria in 4c].
• Patients must consent to the submission of FFPE blocks and/or unstained slides.

Exclusion Criteria:

• Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma.
• Patients must not have peripheral neuropathy ≥ Grade 2.
• Patients must not have presence of Class III or IV heart failure, according to New York Heart Association Classifications, or a known left ventricular ejection fraction of less than 50%. Note: LVEF evaluation by echocardiogram or multi-gated acquisition scan (MUGA) is not required prior to registration.
• Patients must not have a significant history of bleeding events. Patients with a history of a significant bleeding episode (e.g. hemoptysis, upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled by trans-urethral resection of the bladder tumor) within 6 months of registration are not eligible.
• No arterial thrombotic events within 6 months of registration, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medical intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block) are ineligible.

Patients who have experienced a deep venous thrombosis or pulmonary embolus within the past 6 months must be on stable therapeutic anticoagulation to be enrolled to this study.

• In the opinion of the treating investigator, the patient must be a candidate to receive gemcitabine/cisplatin treatment.
• Patients must not have aspirin sensitive asthma.
• Patients must not be known to have hypersensitivity to cisplatin, gemcitabine, or celecoxib.
• Patients must not have any incidence of or uncontrolled medical illness (e.g. active cardiac symptoms, active systemic infection, etc.) that would limit the patient's ability to participate in the protocol.
• Patients must not be pregnant or nursing due to the potential teratogenic side effects of the protocol treatment. Women/men of reproductive potential must agree to use an effective contraceptive method during and for 6 months after completing protocol treatment. A negative pregnancy test is required within 7 days prior to registration for women of child-bearing potential.
• Patients are ineligible if they plan on regular use of NSAIDs at any dose more than 2 times per week (on average) or aspirin at more than 325 mg at least three times per week, on average. Low-dose aspirin not exceeding 100 mg/day is permitted. Patients who agree to stop regular NSAIDs or higher dose aspirin are eligible and no wash out period is required.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Celecoxib plus Gemcitabine/Cisplatin chemo; Celecoxib plus Gemcitabine/Cisplatin neoadjuvant chemotherapy	Drug: Celecoxib; Celecoxib (100 mg daily); Drug: Gemcitabine; 1,000 mg/m2 (IV), on Days 1 and 8 of each 21-day cycle. Up to 4 cycles.; Drug: Cisplatin; 70 mg/m2 (IV), on Day 1 of each 21-day cycle. Up to 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mRNA expression in pre- and post-chemotherapy tissues	Up to four 21-day cycles of chemotherapy.
Number and severity of adverse events	Until 30 days after last treatment.

Secondary Outcome Measures

Outcome Measure	Time Frame
Pathological disease stage at cystectomy, including the rate of pT0 and the rate of < pT2.	At surgery, within 70 days after completing chemotherapy
Two-year progression free survival	Up to 2 years
Two-year overall survival	Up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes Cytokeratin 14 and phospho-histone H3 (proliferation markers)	Correlative Objective	Between baseline and treatment completion, up to 154 days
Changes in COX2 IHC staining	Correlative Objective	Through treatment completion, up to 154 days
Changes in gene expression signatures in association with therapeutic response	correlative objective	Through treatment completion, up to 154 days

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Aihua Edward Yen, MD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2024

Study Registration Dates

• First Submitted: May 23, 2016
• First Submitted That Met QC Criteria: August 28, 2016
• First Posted (Estimated): September 1, 2016

Study Record Updates

• Last Update Posted (Actual): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Celecoxib; Bladder Cancer
• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Cyclooxygenase 2 Inhibitors; Celecoxib; Gemcitabine
• Other Study ID Numbers: H-36486

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO