Clinical trial NCT01261728: Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma
Official title: Phase II Study of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy in Patients With High-Grade Upper Tract Urothelial Carcinoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Urothelial Carcinoma
Keywords: Gemcitabine
Cisplatin
Bladder
radical nephroureterectomy
ureterectomy
10-208
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Mayo Clinic
name: Hartford Hospital
First posted: 2010-12-16
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed high-grade upper tract transitional cell carcinoma at MSKCC or a participating site and/or radiographically visible tumor stage T2-T4a N0/X M0 disease with positive selective urinary cytology or high-grade concomitant bladder tumor. Hydronephrosis associated with tumor on 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 ≤ 1.2
  * 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 ≤ 1.3 mg/dL if male or ≤ 1.1 mg/dL if female OR calculated creatinine clearance ≥ 55 ml/min/1.73m\^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.

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 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.
* 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

Primary outcomes:
measure: To define the pathologic response rate (<pT2)
timeFrame: The time to disease progression is measured from the time of initiation of chemotherapyuntil the first date that systemic recurrence is objectively documented.
Secondary outcomes:
measure: To determine the time to disease progression
timeFrame: 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.
measure: To determine overall survival of patients
timeFrame: 3 years
measure: To evaluate the safety and tolerability
timeFrame: every 2 weeks per cycle
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic - Arizona
state: Arizona
city: Hartford
country: United States
facility: Hartford Hospital (Data Collection Only)
state: Connecticut
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center @ Suffolk
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Uniondale
country: United States
facility: Memorial Sloan Kettering Nassau (Consent and Follow-Up only)
state: New York
city: Allentown
country: United States
facility: Lehigh Valley Health Network (Data Collection Only)
state: Pennsylvania
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Jonathan Coleman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hird AE, Magee DE, Cheung DC, Sander B, Sridhar S, Nam RK, Kulkarni GS. Neoadjuvant Versus Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Microsimulation Model. Clin Genitourin Cancer. 2021 Apr;19(2):e135-e147. doi: 10.1016/j.clgc.2020.10.001. Epub 2020 Oct 13.