SeqUential GeMcitabine and MITomycin Treatment for Favorable High-Risk Upper Urinary Tract Urothelial Carcinoma

Inclusion Criteria: * Subjects must meet all of the following applicable inclusion criteria to participate in the study: 1. Patient has signed Informed Consent Form and is willing and able to comply with all requirements of the protocol. 2. Patient is at least 18 years of age. 3. Naive or recurrent patients with High Grade Ta +/- CIS, non-invasive UTUC in the upper tract (pyelocalyceal system or ureter). * Histologic confirmation with biopsy is necessary. * All patients must undergo ureteroscopy with biopsy. * Non-Invasive Papillary Carcinoma (HGTa) lesions must be maximally ablated with ≤ 15 mm residual papillary disease in total. 4\. Favorable high-grade upper tract urothelial carcinoma (UTUC) as per American Urological Association (AUA) risk stratification below (except that multifocality, obstruction, ureteral involvement, bladder involvement will be allowed). 1. If the bladder is involved with NMIBC it should be treated prior to or during Gem/Jel treatments. 5\. Patients with ECOG (Eastern Cooperative Oncology Group) performance status \<3 (with Karnofsky \>40). 6\. Patients with life expectancy greater than 24 months at time of screening. 7. Patient has no active urinary tract infection (UTI) as confirmed by urine culture or urinalysis\*. 8\. Female Patients of childbearing potential\*\*, must have a negative serum pregnancy test at screening and must agree to use two acceptable \& effective methods of contraception\*\*\*, until 6 months post treatment 9. All sexually active male patients must agree to use a condom during intercourse, for at least 48 hours post each instillation. 10\. Male patients who have a partner that is a female of childbearing potential must agree to use two acceptable \& effective methods of contraception until 6 months post treatment. 11\. Patients must not have any other medical condition(s) that make(s) their participation in the study unadvisable in the opinion of the investigator. Exclusion Criteria: Invasive upper tract urothelial carcinoma (suspected cT2-4 on imaging) or lymphadenopathy (cN1-3) Bilateral disease Patient is actively being treated or intends to be treated with systemic chemotherapy during the duration of the trial. 4\. Any other malignancy diagnosed within 2 years of trial entry with the exception of: a. Basal or squamous cell skin cancers, or b. Noninvasive cancer of the cervix, or c. Any other cancer deemed to be of low-risk for progression or patient morbidity during trial period (basal or squamous cell skin cancers, noninvasive cancer of the cervix, prostate cancer under active surveillance, renal cancer under active surveillance). 4\. Administration not feasible via nephrostomy tube. 5. Inability to deliver the investigational drug to the pyelocalyceal system. 6. Patient has any other medical or mental condition(s) that make(s) his/her participation in the trial unadvisable in the opinion of the treating urologist. 7\. Patient has contraindication to mitomycin C (MMC )treatment, or known sensitivity to MMC. 8\. Patient has an intractable bleeding disorder (e.g., coagulation factors deficiencies, Von Willebrand Disease). 9\. Patient is currently receiving any other investigational agents or has participated in a research protocol involving administration of an investigational product within the past 30 days prior to Visit 1. 10\. Pregnant (positive serum pregnancy test), planning to become pregnant during the trial period, breast-feeding, or of childbearing potential and not practicing reliable contraception\*\*\*. \* In case of a symptomatic UTI the patient will be treated with a full course of antibiotics, and the instillation will be postponed until resolution. In the case of asymptomatic bacteriuria, the use of prophylactic antibiotics and postponement of the treatment is left to the discretion of the PI. \*\* Women of non-childbearing potential: 1. At least 12 months since the last menses, or 2. Without uterus and/or both ovaries, or 3. Has been surgically sterile for at least 6 months prior to trial drug administration. * Acceptable methods of birth control which are considered to have a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectable, combined (estrogen/progesterone) oral contraceptives, intrauterine devices (IUDs-only hormonal), condoms with spermicide, sexual abstinence or vasectomized partner.