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Trial of Paclitaxel Plus Gemcitabine and Cisplatin in Bladder Cancer

Primary Purpose

Urinary Bladder Neoplasms

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Gemcitabine

Paclitaxel

Cisplatin

About this trial

This is an interventional treatment trial for Urinary Bladder Neoplasms focused on measuring Urothelial Cancer, Bladder Cancer, Metastatic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

UTHealth Memorial Hermann Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Combination chemotherapy

Arm Description

Combination chemotherapy consisting of gemcitabine and cisplatin plus paclitaxel on a 21-day cycle.

Outcomes

Primary Outcome Measures

Efficacy as Measured by the Objective Response Rate (ORR).

Objective Response Rate (ORR) is defined as the proportion of patients achieving either a complete response or a partial response based on imaging at any time during the study. Complete response or partial response is based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Secondary Outcome Measures

Safety of Drug Regimen as Measured by Number of Adverse Events

Toxicity assessment will be observational. Numbers and types of events will be quantified and graded according to CTCAE.

Efficacy as Measured by Number Who Progressed

Progression is defined using RECIST 1.1 criteria: " At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)."

Full Information

NCT ID

NCT02560038

First Posted

September 17, 2015

Last Updated

November 2, 2018

Sponsor

The University of Texas Health Science Center, Houston

1. Study Identification

Unique Protocol Identification Number

NCT02560038

Brief Title

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

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Terminated

Why Stopped

slow enrollment; resource re-allocation

Study Start Date

October 2015 (undefined)

Primary Completion Date

September 14, 2017 (Actual)

Study Completion Date

September 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

The University of Texas Health Science Center, Houston

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Urinary Bladder Neoplasms

Keywords

Urothelial Cancer, Bladder Cancer, Metastatic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

3 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Combination chemotherapy

Arm Type

Experimental

Arm Description

Combination chemotherapy consisting of gemcitabine and cisplatin plus paclitaxel on a 21-day cycle.

Intervention Type

Drug

Intervention Name(s)

Gemcitabine

Other Intervention Name(s)

Gemzar

Intervention Description

1000 mg/m2 will be administered as an IV infusion over 10 mg/minute on Days 1 and 8 of each cycle (each cycle is 21 days).

Intervention Type

Drug

Intervention Name(s)

Paclitaxel

Other Intervention Name(s)

Taxol

Intervention Description

175 mg/m2 will be administered as an IVPB over 3 hours on Day 2 of each cycle (each cycle is 21 days).

Intervention Type

Drug

Intervention Name(s)

Cisplatin

Other Intervention Name(s)

Platinol

Intervention Description

70 mg/m2 will be administered as an IVPB over 2 hours on Day 2 of each cycle (each cycle is 21 days).

Primary Outcome Measure Information:

Title

Efficacy as Measured by the Objective Response Rate (ORR).

Description

Time Frame

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 Outcome Measure Information:

Title

Safety of Drug Regimen as Measured by Number of Adverse Events

Description

Toxicity assessment will be observational. Numbers and types of events will be quantified and graded according to CTCAE.

Time Frame

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

Title

Efficacy as Measured by Number Who Progressed

Description

Time Frame

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert J Amato, DO

Organizational Affiliation

The University of Texas Health Science Center, Houston

Official's Role

Principal Investigator

Facility Information:

Facility Name

UTHealth Memorial Hermann Cancer Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Trial of Paclitaxel Plus Gemcitabine and Cisplatin in Bladder Cancer

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