Clinical trial NCT02560038: Trial of Paclitaxel Plus Gemcitabine and Cisplatin in Bladder Cancer
Official title: Phase II Trial of Paclitaxel Plus Gemcitabine and Cisplatin in Urothelial Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Urinary Bladder Neoplasms
Keywords: Urothelial Cancer
Bladder Cancer
Metastatic
Lead sponsor: The University of Texas Health Science Center, Houston
Sponsor class: OTHER
First posted: 2015-09-25
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This trial is for people with bladder cancer that has spread. The purpose of this research study is to see if the chemotherapy combination of gemcitabine and cisplatin plus paclitaxel is safe and effective treatment for bladder cancer.

Paclitaxel, gemcitabine and cisplatin have all been approved by the United States Food and Drug Administration (FDA). Gemcitabine and cisplatin is a standard treatment for bladder cancer. There have been studies that show that paclitaxel and cisplatin have antitumor activity in bladder cancer. European researchers studied paclitaxel, gemcitabine and cisplatin (same drug combination in this trial) and found that the combination provided good disease control and was well tolerated. Investigators are studying the same drug combination, but at different dosages and schedule.

Detailed description: The rationale of the present study is to develop a combination based on the pharmacokinetics and mechanisms of action of the agents paclitaxel plus gemcitabine and cisplatin, which are all known active agents in urothelial tumors. Gemcitabine may be synergistic with DNA-damaging drugs such as paclitaxel and cisplatin because it can antagonize DNA repair. Investigators will investigate the combination in this Phase II study.

Eligibility criteria: Inclusion Criteria:

* All patients must have histologic demonstration of metastatic or locally unresectable transitional cell carcinoma of the urothelium. Minor components (\<50% overall) of variants such as glandular or squamous differentiation, or evolution to more aggressive phenotypes, such as sarcomatoid, or small cell changes are acceptable. However, when these atypical histologies are dominant, other treatment approaches may be more appropriate, and such patients are not eligible.
* All patients must have measurable or evaluable disease. In general, liver and lung lesions should be at least 1 cm, and patients with node-only disease should have lesions of ≥ 1.5 cm in the largest dimension. Patients with disease confined to bone may be eligible if a measurable lytic defect is present. Patients with a 3-dimensional mass or pelvic sidewall fixation on bladder examination under anesthesia are considered to have measurable disease.
* All patients must have adequate physiologic reserves as evidenced by:
* Life expectancy of at least 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
* No clinical history of heart disease and a normal EKG or an ejection fraction measured by echocardiogram or MUGA scan of at least 45%.
* Transaminase less than twice the upper limit of normal. Bilirubin \<1.5 mg%.
* Serum creatinine ≤2.0 mg/dL. Patients presenting with obstructive uropathy may be eligible if they show excellent response to nephrostomy drainage.
* Absolute neutrophil count ≥1500; platelet count ≥100,000.
* Patients must not have had any previous systemic chemotherapy for bladder cancer, including neoadjuvant or adjuvant treatment given remotely. Gemcitabine/cisplatin is the standard of care for metastatic urothelial cancer. Patients who have received treatment would be either resistant or refractory to additional doses. In addition, they would have residual adverse effects from treatment and would be particularly susceptible to further neuropathic adverse events. Any prior intravesicular therapy is allowed.
* Women of childbearing potential must have a negative pregnancy test prior to starting therapy. Men and women of childbearing potential must be willing to consent using effective contraceptive while on treatment and for a reasonable period thereafter.
* Patients must not have an active, or likely to become active, second malignancy.
* Patients must be at least 6 weeks out from pelvic irradiation, and must not have had more than 10% of the bone marrow irradiated.

Exclusion Criteria:

* Patients with uncontrolled CNS metastasis are not eligible.
* Patients with a history of peripheral neuropathy greater than grade 1 are not eligible.
* Pregnant women are excluded.

Primary outcomes:
measure: Efficacy as Measured by the Objective Response Rate (ORR).
timeFrame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months
Secondary outcomes:
measure: Safety of Drug Regimen as Measured by Number of Adverse Events
timeFrame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months
measure: Efficacy as Measured by Number Who Progressed
timeFrame: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 6 months
Other outcomes:
Locations:
city: Houston
country: United States
facility: UTHealth Memorial Hermann Cancer Center
state: Texas
Study officials:
affiliation: The University of Texas Health Science Center, Houston
name: Robert J Amato, DO
role: PRINCIPAL_INVESTIGATOR
References: