Clinical Trial Of Neoadjuvant Chemotherapy (NAC)In Upper Tract Urothelial Carcinoma (UTUC)
Condition: Urothelial Cancer; Bladder Cancer
MeSH terms: Carcinoma, Transitional Cell
Intervention: Neoadjuvant Cisplatin and Gemcitabine
Intervention description: Cisplatin 70 mg/m2 through IV for 60 minutes on day 1 of each cycle. Gemcitabine 1,000 mg/m2 IV for 30 minutes on days 1 and 8 during each cycle. Treatment is expected to continue for up to 4 cycles. Chemotherapy will be followed by radical nephroureterectomy within 6 weeks (+/- 2 weeks) from the last date of chemotherapy.
Intervention MeSH terms: Gemcitabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Urothelial; Bladder; Cancer

Summary:

      The main purpose of this study is to look at the cancer-free survival at two years of
      subjects with high risk upper tract urothelial cancer when treated with the combination of
      two chemotherapy drugs called Gemcitabine and Cisplatin followed by surgery to remove the
      kidney, all or part of the ureter (ureters are tubes made of smooth muscle fibers that propel
      urine from the kidneys to the urinary bladder), and a cuff of bladder where the ureter drains
      into the bladder. Other purposes of the study include looking at the safety of Gemcitabine
      and Cisplatin before surgery for this type of cancer, time to recurrence of cancer, and
      overall survival.

      Exploratory integrative tumor sequencing:

      The purpose of this part of the study is to test deoxyribonucleic acid (DNA) and ribonucleic
      acid (RNA) in various types of samples (tissue and blood) to detect different types of cancer
      genetic changes in upper tract urothelial cancer (UTUC) to help develop future studies in
      UTUC. DNA and RNA contain key instructions for cell function and help determine the
      characteristics of each individual such as hair, eye, and skin color, height, susceptibility
      to diseases, and other characteristics.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have HIGH GRADE upper tract urothelial carcinoma

          -  Patients must be considered to be a candidate for surgery with curative intent
             (nephroureterectomy or distal ureterectomy) with lymph node dissection by the treating
             urologist at baseline within 42 days prior to registration.

          -  Patients must be able to care for themselves and must be up and about more than 50% of
             waking hours

          -  All patients must be evaluated by a medical oncologist at baseline within 42 days
             prior to registration. Patients must be considered to be a candidate for
             cisplatin-based neoadjuvant chemotherapy by a medical oncologist at baseline and must
             have adequate kidney function and any pre-existing peripheral neuropathy must be
             moderate to mild.

          -  Prior uro-oncologic history:

               -  History of or active non-invasive carcinoma or carcinoma in situ of the bladder
                  or upper tract is allowed.

               -  Patients may have received prior intravesical chemotherapy or immunotherapy such
                  as BCG.

               -  Prior neoadjuvant chemotherapy for bladder cancer or invasive contralateral upper
                  tract cancer is allowed.

               -  Prior adjuvant chemotherapy for bladder cancer or invasive contralateral upper
                  tract cancer is allowed but must have been completed ≥2 years prior to study
                  registration.

          -  Patients must have adequate organ and bone marrow function as determined by screening
             tests

          -  Patients must have recovered from any reversible toxicities of prior procedure or
             surgery

          -  Patients must be 18 years or older on date of registration

          -  All patients must be informed of the investigational nature of this study and must
             sign an informed consent document

        Exclusion Criteria:

          -  Patients must have no evidence of regional lymphadenopathy or distant metastasis on
             imaging.

          -  No history of invasive or node positive or metastatic bladder cancer or invasive
             contralateral upper tract cancer within 2 years prior to registration.

          -  Patients with one kidney are not eligible

          -  Patients may not be enrolled in another interventional clinical trial at the time of
             registration.

          -  No prior non-urothelial malignancy is allowed, except for cancer from which the
             patient has been disease free for at least 1 year at the discretion of the treating
             oncologist. History of adequately treated (at the discretion of the treating
             oncologist) basal cell or squamous cell skin cancer or in situ cervical cancers is
             allowed.

          -  Pregnant or lactating women are not eligible. Women/men of reproductive potential must
             agree to use an effective contraceptive method. Women with reproductive potential must
             have a negative pregnancy test within 14 days prior to registration.

          -  Patients must not have any other medical condition(s) that make(s) their participation
             in the study unadvisable in the opinion of the treating oncologist.