Gemcitabine Hydrochloride and Cisplatin in Treating Patients with High-Grade Urothelial Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IITreatmentActive18 and over10-208
NCI-2010-02376, NCT01261728

Trial Description

Summary

This phase II trial studies how well giving gemcitabine hydrochloride together with cisplatin before surgery work in treating patients with high-grade urothelial cancer. Drugs used in chemotherapy, such as gemcitabine hydrochloride and cisplatin (GC), work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

Further Study Information

PRIMARY OBJECTIVES:

I. To define the pathologic response rate (< pT2) of neoadjuvant GC regimen in patients with upper tract high-grade urothelial carcinoma.

SECONDARY OBJECTIVES:

I. To determine the time to disease progression in patients with upper tract high-grade urothelial carcinoma with neoadjuvant GC followed by radical nephroureterectomy.

II. To determine overall survival of patients with upper tract high-grade urothelial carcinoma treated with neoadjuvant GC followed by radical nephroureterectomy.

III. To evaluate the safety and tolerability of neoadjuvant GC in this setting.

OUTLINE:

Patients receive gemcitabine hydrochloride intravenously (IV) over approximately 30 minutes and cisplatin IV over approximately 30 minutes on days 1 and 8. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Within 12 weeks of chemotherapy completion, patients undergo nephroureterectomy as determined by their attending surgical urologic oncologist.

After completion of study treatment, patients are followed up every 3 months for 18 months, every 6 months for 18 months, and then yearly thereafter.

Eligibility Criteria

Inclusion Criteria:

Histologically confirmed high-grade upper tract transitional cell carcinoma at Memorial Sloan-Kettering Cancer Center (MSKCC) or a participating site and/or radiographically visible tumor stage T2-T4a N0/X M0 disease with positive selective urinary cytology; hydronephrosis associated with tumor on imaging or biopsy will be considered invasive by definition

Medically appropriate candidate for radical nephroureterectomy or ureterectomy as per MSKCC or a participating site attending urologic oncologist

Karnofsky performance status >= 70%

Absolute neutrophil count >= 1500 cells/mm^3

Platelets >= 100,000 cells/mm^3

Hemoglobin >= 9.0 g/dL

Bilirubin =< 1.5

Aspartate transaminase (AST) and alanine transaminase (ALT) =< 2.5 x upper limit of normal (ULN) for the institution

Alkaline phosphatase =< 2.5 x ULN for the institution

Serum creatinine =< 1.5 mg/dL and calculated creatinine clearance >= 55 ml/min/1.73 m^2

If female of childbearing potential, serum pregnancy test is negative

Patients with reproductive potential must use an effective method to avoid pregnancy for the duration of the trial

Exclusion Criteria:

Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and surgically resectable

Presence or history of carcinoma in situ (CIS)

Prior systemic chemotherapy (prior intravesical therapy is allowed)

Prior radiation therapy to the bladder

Evidence of New York Heart Association (NYHA) functional class III or IV heart disease

Serious intercurrent medical or psychiatric illness, including serious active infection

Preexisting sensory grade 3 neuropathy

Major surgery or radiation therapy < 4 weeks of starting study treatment

Concomitant use of any other investigational drugs

Any of the following within the 6 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, or pulmonary embolism

Ongoing cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade >= 2

Uncontrolled hypertension (> 150/100 mmHg despite optimal medical therapy)

Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or other active infection; patients with HIV but no evidence of AIDS will be considered candidates

Concurrent treatment on another clinical trial; supportive care trials or non-treatment trials, e.g. quality of life (QOL), are allowed

Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin (low dose warfarin up to 2 mg orally [PO] daily or use of subcutaneous low molecular weight heparin for thromboembolic prophylaxis is allowed)

Pregnancy or breast-feeding; patients must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy; the definition of effective contraception will be based on the judgment of the MSKCC and participating site principal investigator (PI); male patients must be surgically sterile or agree to use effective contraception

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Memorial Sloan-Kettering Cancer Center

  • National Cancer Institute
Jonathan Andrew Coleman, Principal Investigator

Trial Sites

U.S.A.

Arizona
Scottsdale

Mayo Clinic in Arizona

Thai Huu Ho
Ph: 480-301-8000

Thai Huu Ho
Principal Investigator

Connecticut
Hartford

Hartford Hospital

Anoop Mohan Meraney
Email: Anoop.Meraney@hhchealth.org

Anoop Mohan Meraney
Principal Investigator

New York
New York

Memorial Sloan-Kettering Cancer Center

Jonathan Andrew Coleman
Ph: 646-422-4432
Email: colemanj@mskcc.org

Jonathan Andrew Coleman
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01261728

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.