Gemcitabine Hydrochloride and Cisplatin Before Surgery in Treating Patients With Muscle Invasive Bladder Cancer

• Sponsor: Fox Chase Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01611662
• Collaborator: (none)
• Enrollment: 32
• Locations: 2
• Arm: 1
• Actual Duration (Months): 79.8
• Patients Per Site: 16
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this research study is to find out what effects, good and/or bad, dose-dense (every 14 days) chemotherapy with gemcitabine (gemcitabine hydrochloride) and cisplatin given before surgery have on patients and their muscle invasive bladder cancer.

Condition or Disease	Intervention/Treatment	Phase
Distal Urethral Cancer; Proximal Urethral Cancer; Squamous Cell Carcinoma of the Bladder; Stage II Bladder Cancer; Stage III Bladder Cancer; Urethral Cancer Associated With Invasive Bladder Cancer	Drug: gemcitabine hydrochloride; Drug: cisplatin; Procedure: therapeutic conventional surgery; Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the rate of complete response (pT0) at cystectomy following preoperative dose dense gemcitabine and cisplatin (DD GC) in patients with muscle invasive urothelial carcinoma of the bladder.

SECONDARY OBJECTIVES:

1. To assess the toxicity profile of DD GC when given in the neoadjuvant setting: To define the number of patients who complete all three cycles of treatment without dose reduction, and to describe the incidence of toxicity.

2. To assess the 5 year overall and relapse free survival in patients who receive neoadjuvant DD GC.

TERTIARY OBJECTIVES:

1. To evaluate tissue specimens from patients to assess for molecular markers that correlate with clinical outcome.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy.

After completion of study treatment, patients are followed up for 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Neoadjuvant Dose Dense Gemcitabine and Cisplatin In Muscle Invasive Bladder Cancer
• Actual Study Start Date: May 29, 2012
• Actual Primary Completion Date: Jul 12, 2013
• Actual Study Completion Date: Jan 22, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (gemcitabine hydrochloride, cisplatin, surgery) Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy.	Drug: gemcitabine hydrochloride; Given IV; Other Names: dFdC difluorodeoxycytidine hydrochloride gemcitabine Gemzar ; Drug: cisplatin; Given IV; Other Names: CACP CDDP CPDD DDP ; Procedure: therapeutic conventional surgery; Undergo radical cystectomy; Other: laboratory biomarker analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Pathological Complete Response Rate Following Chemotherapy Before Surgery [Up to 5 years]

   Pathological response rate following neoadjuvant chemotherapy was assessed by TNM staging at the time of radical cystectomy

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have histologically confirmed urothelial carcinoma of the bladder or urethra; patients with urothelial carcinoma of the prostatic urethra only may be included at primary investigator (PI) discretion; T-stage must be T2 to T4a; patients with radiographic N0 disease or N1 disease are eligible for the study; patients must not have radiographic evidence of metastatic disease; mixed histologies which are predominantly urothelial, such as with squamous or micropapillary differentiation, are allowed so long as there is no component of small cell histology; histology must be confirmed by a pathologist at an institution involved in this study

• Patients must be candidates for radical cystectomy with the goal of cure

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Leukocytes >= 3,000/mcL

• Absolute neutrophil count >= 1,500/mcL

• Platelets >= 100,000/mcL

• Total bilirubin =< institutional upper limit of normal (ULN)

• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT)(serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN

• Patients must have adequate renal function defined as creatinine clearance >= 50 mL/min; for eligibility, creatinine clearance may be either calculated using the Cockcroft-Gault formula or measured with 24 hour urine collection; note that 24 hour urine collection is required at baseline, but does not have to be used for eligibility if calculated clearance by Cockcroft-Gault is preferred; nephrostomy or ureteral stent placement in order to achieve adequate creatinine clearance is allowed

• Women of child-bearing potential (WOCBP) and men with a female partner who is a WOCBP must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) starting prior to beginning treatment and continuing until at least 3 months after last dose of chemotherapy and surgery; should a woman become pregnant or suspect she is pregnant while participating in this study or if a female partner of a man participating in this study becomes pregnant, the treating physician must be notified immediately; WOCBP must have a negative serum or urine pregnancy test within 7 days prior to initiating study treatment

• No other active malignancy

• Ability to understand and the willingness to sign written informed consent and Health Insurance Portability and Accountability Act (HIPAA) documents

Exclusion Criteria:

• Patients who have had intravesicular therapy within 4 weeks of study entry, or those who have not recovered from adverse effects of such agents administered more than 4 weeks earlier

• Patients may not be receiving any investigational agents within 4 weeks of study entry

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to gemcitabine or cisplatin or other agents used in the study

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Pregnant women are excluded from this study

• Known human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

• Patients who have undergone prior radiation to greater than or equal to 25% of the bone marrow within the past year are excluded

• Patients who have received any previous systemic chemotherapy or radiation therapy for urothelial carcinoma within 1 year of study entry are ineligible

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Thomas Jefferson University, Kimmel Cancer Center	Philadelphia	Pennsylvania	United States	19107
2	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111-2497

Sponsors and Collaborators

• Fox Chase Cancer Center

Investigators

• Principal Investigator: Elizabeth Plimack, Fox Chase Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Fox Chase Cancer Center
• ClinicalTrials.gov Identifier: NCT01611662
• Other Study ID Numbers: ERP-GU-052; NCI-2012-00906; IRB#12-015; ERP-GU-052
• First Posted: Jun 5, 2012
• Last Update Posted: Jul 29, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Urinary Bladder Neoplasms; Urethral Neoplasms; Gemcitabine

Study Results

Participant Flow

Arm/Group Title	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. gemcitabine hydrochloride: Given IV cisplatin: Given IV therapeutic conventional surgery: Undergo radical cystectomy laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
STARTED	32
COMPLETED	31
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. gemcitabine hydrochloride: Given IV cisplatin: Given IV therapeutic conventional surgery: Undergo radical cystectomy laboratory biomarker analysis: Correlative studies
Overall Participants	31
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69
Sex: Female, Male (Count of Participants)
Female	10 32.3%
Male	21 67.7%
Baseline clinical stage (Count of Participants)
T2N0M0	11 35.5%
T3N0M0	15 48.4%
T4aN0Mo/TxN1M0	5 16.1%

Outcome Measures

1. Primary Outcome

Title	Pathological Complete Response Rate Following Chemotherapy Before Surgery
Description	Pathological response rate following neoadjuvant chemotherapy was assessed by TNM staging at the time of radical cystectomy
Time Frame	Up to 5 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. gemcitabine hydrochloride: Given IV cisplatin: Given IV therapeutic conventional surgery: Undergo radical cystectomy laboratory biomarker analysis: Correlative studies
Measure Participants	31
Number (95% Confidence Interval) [percentage of participants]	32 103.2%

Adverse Events

Arm/Group Title	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
Arm/Group Description	Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and cisplatin IV on day 1 or divided over days 1 and 2. Treatment repeats every 14 days for 3 courses in the absence of disease progression or unacceptable toxicity. Beginning 3-8 weeks after chemotherapy, patients undergo radical cystectomy. gemcitabine hydrochloride: Given IV cisplatin: Given IV therapeutic conventional surgery: Undergo radical cystectomy laboratory biomarker analysis: Correlative studies
All Cause Mortality
	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
	Affected / at Risk (%)	# Events
Total	16/31 (51.6%)
Blood and lymphatic system disorders
Acute Renal Insufficiency	1/31 (3.2%)
cerebral Infarction	1/31 (3.2%)
Cardiac disorders
Chest pain	2/31 (6.5%)
Coronary Artey Disease	1/31 (3.2%)
Myocardial Infarction	1/31 (3.2%)
Atrial Fibrillation	1/31 (3.2%)
Gastrointestinal disorders
Constipation	1/31 (3.2%)
Nausea	1/31 (3.2%)
vomiting	2/31 (6.5%)
Ileus	1/31 (3.2%)
General disorders
Fever	3/31 (9.7%)
Infections and infestations
infected lymphocele	1/31 (3.2%)
bacteremia	1/31 (3.2%)
Metabolism and nutrition disorders
Dehydration	1/31 (3.2%)
hyperkalemia	2/31 (6.5%)
hypernatremia	1/31 (3.2%)
hyperglycemia	1/31 (3.2%)
Musculoskeletal and connective tissue disorders
Gout	1/31 (3.2%)
Renal and urinary disorders
Acute Kidney Injury	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
dyspnea	1/31 (3.2%)
pneumonia	1/31 (3.2%)
hemoptysis	1/31 (3.2%)
Vascular disorders
Deep Vein Thrombosis	2/31 (6.5%)
hypotension	1/31 (3.2%)
Pulmonary embolism	1/31 (3.2%)
Other (Not Including Serious) Adverse Events
	Treatment (Gemcitabine Hydrochloride, Cisplatin, Surgery)
	Affected / at Risk (%)	# Events
Total	31/31 (100%)
Blood and lymphatic system disorders
Anemia	29/31 (93.5%)
Cardiac disorders
Atrial Fibrilation	1/31 (3.2%)
Chest pain	2/31 (6.5%)
Myocardial Infarction	1/31 (3.2%)
Sinus Brachycardia	1/31 (3.2%)
Sinus Trachycardia	4/31 (12.9%)
Cardiac Faliure	1/31 (3.2%)
Acute coronary syndrome	1/31 (3.2%)
Ear and labyrinth disorders
Hearing Impaired	1/31 (3.2%)
Eye disorders
Blurred Vision	1/31 (3.2%)
Tinnitus	6/31 (19.4%)
Glaucoma	1/31 (3.2%)
Gastrointestinal disorders
Constipation	14/31 (45.2%)
Diarrhea	6/31 (19.4%)
Dysphagia	1/31 (3.2%)
GERD	2/31 (6.5%)
Ileus	4/31 (12.9%)
Mucositis	4/31 (12.9%)
Nausea	24/31 (77.4%)
vomiting	5/31 (16.1%)
Flatulence	1/31 (3.2%)
General disorders
chills	5/31 (16.1%)
Edema	6/31 (19.4%)
fatigue	30/31 (96.8%)
fever	5/31 (16.1%)
flu-like symptoms	2/31 (6.5%)
infusion related reaction	2/31 (6.5%)
Injection site reaction	3/31 (9.7%)
extravasation	1/31 (3.2%)
Infusion site extravasation	2/31 (6.5%)
Infections and infestations
Sepsis	1/31 (3.2%)
Urinary tract infection	4/31 (12.9%)
Skin Infection	1/31 (3.2%)
Phlebitis	2/31 (6.5%)
intra-abdominal infection	1/31 (3.2%)
Investigations
AST/SGOT	3/31 (9.7%)
ALT/SGPT	4/31 (12.9%)
Alkaline Phosphatase increased	15/31 (48.4%)
blood bilirubin increased	1/31 (3.2%)
creatinine increased	15/31 (48.4%)
White blood cells decreased	4/31 (12.9%)
ANC decreased	4/31 (12.9%)
Platelet count decreased	9/31 (29%)
lymphocyte count decreased	13/31 (41.9%)
cardiac troponin increased	3/31 (9.7%)
Weight loss	2/31 (6.5%)
Dehydration	2/31 (6.5%)
Metabolism and nutrition disorders
Hypoalbuminemia	11/31 (35.5%)
Hypocalcemia	12/31 (38.7%)
Hyperkalemia	12/31 (38.7%)
Hypokalemia	14/31 (45.2%)
Hypernatremia	8/31 (25.8%)
Hyponatremia	10/31 (32.3%)
Hypophosphatemia	3/31 (9.7%)
Hyperglycemia	24/31 (77.4%)
Hypoglycemia	1/31 (3.2%)
Hypomagnesium	16/31 (51.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/31 (16.1%)
Generalized muscle weakness	3/31 (9.7%)
Pain in extremity	3/31 (9.7%)
Flank pain	3/31 (9.7%)
Nervous system disorders
Dizziness	5/31 (16.1%)
Dysgeusia	8/31 (25.8%)
Headache	3/31 (9.7%)
Peripheral sensory neuropathy	5/31 (16.1%)
Psychiatric disorders
Anxiety	12/31 (38.7%)
Depression	1/31 (3.2%)
Insomnia	3/31 (9.7%)
Restlessness	1/31 (3.2%)
Renal and urinary disorders
Hematuria	3/31 (9.7%)
Proteinuria	3/31 (9.7%)
Urinary frequency	10/31 (32.3%)
Acute kidney injury	2/31 (6.5%)
urinary retention	1/31 (3.2%)
Reproductive system and breast disorders
pelvic pain	1/31 (3.2%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/31 (3.2%)
Cough	2/31 (6.5%)
Dyspnea	3/31 (9.7%)
Epistaxis	1/31 (3.2%)
Hiccups	2/31 (6.5%)
Skin and subcutaneous tissue disorders
Alopecia	6/31 (19.4%)
Rash	1/31 (3.2%)
Vascular disorders
Hypertension	9/31 (29%)
Hypotension	4/31 (12.9%)
Thromboembolic event	3/31 (9.7%)
lymphocele	1/31 (3.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.