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

This study is currently recruiting participants.
Verified January 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: January 27, 2014
Last verified: January 2014

December 15, 2010
January 27, 2014
December 2010
December 2014   (final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT01261728 on ClinicalTrials.gov Archive Site
  • 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.
  • 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 3.0.
Not Provided
Not Provided
 
Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma
Phase II Study of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Urothelial Carcinoma
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.
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.
Intervention: Drug: Gemcitabine and Cisplatin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
54
December 2014
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: Jonathan Coleman, MD 646-422-4432
Contact: Dean Bajorin, MD 646-422-4333
United States
 
NCT01261728
10-208
Not Provided
Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
  • Mayo Clinic in Arizona
  • Hartford Hospital
Principal Investigator: Jonathan Coleman, MD Memorial Sloan-Kettering Cancer Center
Memorial Sloan-Kettering Cancer Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP