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Gemcitabine and Docetaxel for the Treatment of Patients with Bladder Cancer

Trial Status: Active

This phase II trial studies the effect of gemcitabine and docetaxel given directly into the bladder in treating patients with non-muscle invasive bladder cancer patients who have had no prior treatment with bacillus Calmette-Guerin (BCG) (BCG-naive), the current standard of care. Chemotherapy drugs, such as gemcitabine and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Inclusion Criteria

  • 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 European Organization for Research and Treatment of Cancer (EORTC) risk criteria summarized as follows: * 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) * Intermediate-risk tumors: All tumors not defined in the two adjacent categories (between the category of low- and high-risk) * 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 on Ta low-grade tumors) * NOTE #1: Low-risk tumors as defined above are not eligible * NOTE #2: Mixed histologies are permitted, provided a component of urothelial carcinoma is present * NOTE #3: All patients with high-grade T1 (HGT1) should undergo a restaging TURBT
  • Eastern Cooperative Oncology Group (ECOG) (World Health Organization [WHO]) performance status 0,1, or 2
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for 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: * 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 * 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)
  • Subjects who give a written informed consent obtained according to local guidelines

Exclusion Criteria

  • 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: * Abdomen/pelvis – computed tomography (CT) scan * Chest – chest x-ray or CT scan
  • Subjects with concurrent upper urinary tract (i.e. ureter, renal pelvis) urothelial carcinoma of any stage. (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)
  • 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
  • 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
  • Subjects who have had radiotherapy =< 4 weeks prior to starting study drug, or who have not recovered from radiotherapy toxicities
  • Pregnant or breast-feeding women
  • Subjects unwilling or unable to comply with the protocol
  • Patients with prior systemic gemcitabine or docetaxel use for a non-bladder malignancy may enroll and receive treatment

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: Max Kates
Phone: 410-614-0009

PRIMARY OBJECTIVE:

I. Determine the complete response (CR) rate of non-muscle invasive bladder cancer (NMIBC) subjects treated with intravesical gemcitabine/docetaxel.

SECONDARY OBJECTIVES:

I. Determine safety of NMIBC subjects treated with intravesical gemcitabine hydrochloride (gemcitabine)/docetaxel.

II. Determine the 12-month, and 24-month recurrence-free survival (RFS) rates of NMIBC subjects treated with intravesical gemcitabine/docetaxel.

III. Determine the cystectomy free survival rates of NMIBC subjects treated with intravesical gemcitabine/docetaxel.

IV. Determine how variant histology attenuates 12-month RFS and surgical upstaging rates among NMIBC subjects treated with intravesical gemcitabine/docetaxel.

V. To assemble a blood, urine, and tissue bank (with pre and post treatment samples) to assess molecular correlates for response to intravesical gemcitabine/docetaxel (GemDoce).

VI. Determine how ribonucleic acid (RNA) expression changes, including molecular subtypes attenuate 12-month RFS and surgical upstaging rates among NMIBC subjects treated with intravesical gemcitabine/docetaxel.

VII. Determine how tumor deoxyribonucleic acid (DNA) mutations, rearrangements/fusions, copy number alterations, tumor mutational burden impact clinical outcomes (e.g. CR rate, 12-month [12m] RFS, surgical upstaging) among NMIBC subjects treated with intravesical gemcitabine/docetaxel.

VIII. Determine how tumor mutational burden attenuates 12-month RFS and surgical upstaging rates among NMIBC subjects treated with intravesical gemcitabine/docetaxel.

IX. Determine associations between baseline- and post-treatment T lymphocyte subset ratios and 12-month RFS and surgical upstaging rates among NMIBC subjects treated with intravesical gemcitabine/docetaxel.

OUTLINE:

INDUCTION: Patients receive gemcitabine hydrochloride intravesically over 60 minutes once a week (QW) followed by docetaxel intravesically over 60 minutes QW for 6 weeks in the absence of disease progression or unacceptable toxicity.

MAINTENANCE: Patients who respond to induction treatment continue gemcitabine hydrochloride intravesically over 60 minutes once a month and docetaxel intravesically over 60 minutes once a month for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of treatment, patients are followed up at 24 months.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Johns Hopkins University / Sidney Kimmel Cancer Center

Principal Investigator
Max Kates

  • Primary ID J2020
  • Secondary IDs NCI-2020-07519, IRB00241941, CRMS-74022
  • Clinicaltrials.gov ID NCT04386746