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

Brief Title

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

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.
    

Study Phase

Phase 2

Study Type

Interventional

Primary Outcome

To define the pathologic response rate (					

Secondary Outcome

 To determine the time to disease progression

Condition

Urothelial Carcinoma

Intervention

Gemcitabine and Cisplatin

Study Arms / Comparison Groups

 Gemcitabine and Cisplatin

Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Status

Drug

Estimated Enrollment

57

Start Date

December 14, 2010

Completion Date

December 2023

Primary Completion Date

December 2023

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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jonathan Coleman, MD, , 

Location Countries

United States

Location Countries

United States

NCT ID

NCT01261728

Organization ID

10-208

Responsible Party

Sponsor

Study Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

 Mayo Clinic

Study Sponsor

Jonathan Coleman, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center

Verification Date

January 2023