Intravesical Gemcitabine and Docetaxel for BCG naïve Non-muscle Invasive Bladder Cancer
Condition: Urothelial Carcinoma Bladder; Bladder Cancer
MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell
Intervention: Gemcitabine; Docetaxel
Intervention description: 1g gemcitabine in 50ml sterile water; instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.; 37.5mg docetaxel in 50ml normal saline solution (NSS); instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.
Intervention MeSH terms: Gemcitabine; Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NMIBC

Summary:

      A single-arm, two-stage, open-label, phase 2 study investigating the safety and efficacy of
      intravesical gemcitabine/docetaxel for bacillus Calmette-Guerin (BCG)-naïve patients with
      non-muscle invasive bladder cancer (NMIBC).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Histologically confirmed intermediate or high-risk non-muscle invasive urothelial
             carcinoma of the bladder (Ta, T1, or Tis stage) on TURBT obtained within 90 days of
             registration defined according to modified EORTC risk criteria summarized as follows:

               1. Low-risk tumors: Initial or recurrent tumor > 12 months after resection with all
                  of the following:

                    -  Solitary tumor

                    -  Low-grade

                    -  < 3 cm

                    -  No carcinoma in situ (CIS)

               2. Intermediate-risk tumors: All tumors not defined in the two adjacent categories
                  (between the category of low- and high-risk)

               3. High-risk tumors: Any of the following:

                    -  T1 tumor

                    -  High-grade

                    -  CIS

                    -  Multiple and recurrent and large (> 3 cm) Ta low-grade tumors (all
                       conditions must be met for this point of Ta low-grade tumors)

               4. Note #1: Low-risk tumors as defined above are not eligible

               5. Note #2: Mixed histologies are permitted, provided a component of urothelial
                  carcinoma is present

               6. Note #3: All patients with high-grade T1 (HGT1) should undergo a restaging TURBT

          2. Eastern Cooperative Oncology Group (ECOG) (WHO) performance status 0, 1, or 2

          3. Age ≥ 18 years old at time of consent

          4. Evidence of post-menopausal status or negative urinary or serum pregnancy test or
             female pre-menopausal patients is required. Women will be considered post-menopausal
             if they have been amenorrheic for 12 months without an alternative medical cause. The
             following age-specific requirements apply:

               1. Women <50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               2. Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrheic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or
                  hysterectomy).

          5. Subjects who give a written informed consent obtained according to local guidelines.

        Exclusion Criteria:

          1. Subjects with muscle-invasive (i.e. T2, T3, T4), locally advanced unresectable, or
             metastatic urothelial carcinoma as assessed on baseline radiographic imaging obtained
             within 90 days prior to study registration. The required radiographic imaging
             includes:

               1. Abdomen/Pelvis - CT scan

               2. Chest - chest x-ray or CT scan

          2. Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) urothelial
             carcinoma of any stage.

             a. Note: Subjects with history of non-invasive (Ta, Tis) upper tract urothelial
             carcinoma that has been definitively treated with at least one post-treatment disease
             assessment (i.e. cytology, biopsy, imaging) that demonstrates no evidence of residual
             disease are eligible.

          3. Subjects with another active second malignancy with an estimated overall survival from
             the second malignancy of < 12 months. Subjects with another second active malignancy
             that are deemed to have an estimated overall survival of >12 months are eligible.

          4. Subjects who have received the last administration of an anti-cancer therapy including
             chemotherapy, immunotherapy, and monoclonal antibodies ≤ 4 weeks prior to starting
             study drug, or who have not recovered from the side effects of such therapy.

          5. Subjects who have had radiotherapy ≤ 4 weeks prior to starting study drug, or who have
             not recovered from radiotherapy toxicities.

          6. Pregnant or breast-feeding women.

          7. Subjects unwilling or unable to comply with the protocol.

          8. Patients with prior systemic gemcitabine or docetaxel use for a non-bladder malignancy
             may enroll and receive treatment.