Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborators:
Mayo Clinic in Arizona
Hartford Hospital
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01261728
First received: December 15, 2010
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

The purpose of this study is to see if getting chemotherapy with Gemcitabine and Cisplatin for four weeks every 21 days for a total of 12 weeks can help shrink the tumor before undergoing surgery for kidney cancer.


Condition Intervention Phase
Urothelial Carcinoma
Drug: Gemcitabine and Cisplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To define the pathologic response rate (<pT2) [ Time Frame: The time to disease progression is measured from the time of initiation of chemotherapyuntil the first date that systemic recurrence is objectively documented. ] [ Designated as safety issue: No ]
    of neoadjuvant Gemcitabine and Cisplatin regimen in patients with upper tract high-grade urothelial carcinoma. And is defined as the absence of high-grade carcinoma (<pT2 disease) and the absence of microscopic lymph node metastases (N0) on the final nephroureterectomy specimen.


Secondary Outcome Measures:
  • To determine the time to disease progression [ Time Frame: Time to progression is measured from the time of initiation of chemotherapy until the 1st date that systemic recurrence is objectively documented. Systemic recurrence for this trial is defined as either metastatic or local pelvic recurrence. ] [ Designated as safety issue: No ]
    will be estimated using the methods of Kaplan and Meier in patients with upper tract high-grade urothelial carcinoma with neoadjuvant GC followed by radical nephroureterectomy.

  • To determine overall survival of patients [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    will be estimated using the methods of Kaplan and Meier in patients with upper tract high-grade urothelial carcinoma treated with neoadjuvant GC followed by radical nephroureterectomy.

  • To evaluate the safety and tolerability [ Time Frame: every 2 weeks per cycle ] [ Designated as safety issue: Yes ]
    of neoadjuvant Gemcitabine and Cisplatin in this setting. Toxicity will be graded according to the National Cancer Institute Common Toxicity Criteria version 4.0.


Estimated Enrollment: 54
Study Start Date: December 2010
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine and Cisplatin
This is a Phase II Study of Gemcitabine and Cisplatin (GC) as neoadjuvant chemotherapy in patients with upper tract high-grade urothelial carcinoma who are candidates for radical nephroureterectomy or distal ureterectomy.
Drug: Gemcitabine and Cisplatin
Patients will receive four cycles of GC administered every 21 days. Gemcitabine 1,000 mg/m2 and Cisplatin 35 mg/m2 will be administered intravenously on days 1 and 8. A total of four cycles of therapy will be administered at 21 day intervals followed by radical nephroureterectomy or distal ureterectomy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC or a participating site and 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%
  • Age ≥ 18 years of age
  • Required Initial Laboratory Values:

    • Absolute neutrophil count ≥ 1500 cells/mm3
    • Platelets ≥ 100,000 cells/mm3
    • Hemoglobin ≥ 9.0g/dL
    • Bilirubin ≤ 1.5 the upper limit of normal (ULN) for the institution
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for the institution
    • Alkaline phosphatase ≤ 2.5 x ULN for the institution
    • Serum creatinine ≤ 1.5 mg/dL and calculated creatinine clearance ≥ 55 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.

ml/min/1.73m2 using the formula: CKD epi : GFR = 141 X min(Scr/κ,1)α X max(Scr/κ,1)-1.209 X 0.993Age X 1.018 [if female] X 1.159 [if black]

  • Scr is serum creatinine, k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/k or 1, and max indicates the maximum of Scr/k or 1.
  • 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 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 NCI CTCAE Version 4.0 grade ≥ 2.
  • Prolonged QTc interval on baseline EKG (>450 msec for males and >470 msec for females).
  • 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 involving an intervention which may affect the primary endpoint. Supportive care trials or non-treatment trials, e.g. QOL, are allowed.
  • Ongoing treatment with therapeutic doses of warfarin or low molecular weight heparin (low dose warfarin up to 2 mg 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 PI. Male patients must be surgically sterile or agree to use effective contraception
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01261728

Contacts
Contact: Jonathan Coleman, MD 646-422-4432
Contact: Dean Bajorin, MD 646-422-4333

Locations
United States, Arizona
Mayo Clinic in Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85259
Contact: Estrella Carballido, MD         
Principal Investigator: Estrella Carballido, MD         
United States, Connecticut
Hartford Hospital Not yet recruiting
Hartford, Connecticut, United States
Contact: Robert Siegel, MD         
Principal Investigator: Robert Siegel, MD         
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Jonathan Coleman, MD    646-422-4432      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Jonathan Coleman, MD    646-422-4432      
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Jonathan Coleman, MD    646-422-4432      
Contact: Dean Bajornin, MD    646-422-4333      
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Jonathan Coleman, MD    646-422-4432      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Jonathan Coleman, MD    646-422-4432      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Mayo Clinic in Arizona
Hartford Hospital
Investigators
Principal Investigator: Jonathan Coleman, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01261728     History of Changes
Other Study ID Numbers: 10-208
Study First Received: December 15, 2010
Last Updated: July 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Gemcitabine
Cisplatin
Bladder
radical nephroureterectomy
ureterectomy
10-208

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Gemcitabine
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014