Intravesical Gemcitabine and Docetaxel for BCG naïve Non-muscle Invasive Bladder Cancer (GEMDOCE)

A Phase II Trial for the Use of Intravesical Gemcitabine and Docetaxel (GEMDOCE) in the Treatment of BCG naïve Non-muscle Invasive Urothelial Carcinoma of the Bladder

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Bladder Cancer; Urothelial Carcinoma Bladder
• Intervention / Treatment: Drug: Gemcitabine; Drug: Docetaxel

Detailed Description

All participants will receive an induction course of gemcitabine/docetaxel instillations (administered once a week for six consecutive weeks) followed by monthly maintenance instillations if initial efficacy is seen. In addition to providing initial efficacy data, this study will provide safety and long-term efficacy data on the combination regimen studied. A tolerable safety profile and demonstrated efficacy would support a potential, randomized phase 3 trial comparing the experimental combination therapy and standard of care intravesical BCG therapy.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University: Sidney Kimmel Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Intravesical Gemcitabine/Docetaxel; Gemcitabine/Docetaxel induction is given intravesically in sequential order once a week for six consecutive weeks. One gram of gemcitabine in 50 ml of sterile water is slowly instilled into the bladder via a Foley catheter and the catheter is clamped for 60 minutes. The bladder is then drained and 40 mg of docetaxel in 50 ml of NSS is then slowly instilled via the Foley catheter into the bladder. The catheter is again clamped for 60 minutes before draining. If initial efficacy seen, patients will have monthly maintenance instillations of Gemcitabine/Docetaxel.

Drug: Gemcitabine; 1g gemcitabine in 50ml sterile water; instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.; Other Names: Gemzar; Drug: Docetaxel; 37.5mg docetaxel in 50ml normal saline solution (NSS); instilled once weekly for 6 weeks and then once monthly for ≤ 21 months.; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-Month Complete Response Rate	Number of patients with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage as assessed by cystoscopy with biopsy and urine cytology.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-Month Relapse-Free Survival Rate	Proportion of patients alive and with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage.	12 months
24-Month Relapse-Free Survival Rate	Proportion of patients alive and with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage.	24 months
Safety Profile as Assessed by Proportion of Adverse Events by Type	Proportion of adverse events by type, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).	Up to 24 months
Safety Profile as Assessed by Proportion of Adverse Events by Grade	Proportion of adverse events by grade, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).	Up to 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Gene Alterations as Measured by RNA-seq	Number of gene alterations as measured by RNA-seq. Compare results to 3-month Complete Response rate using statistical methods.	3 months
Type of Gene Alterations as Measured by RNA-seq	Type of gene alterations as measured by RNA-seq. Compare results to 3-month Complete Response rate using statistical methods.	3 months
Number of Gene Alterations as Measured by RNA-seq	Number of gene alterations as measured by RNA-seq. Compare results to 12-month Relapse-Free Survival rate using statistical methods.	12 months
Type of Gene Alterations as Measured by RNA-seq	Type of gene alterations as measured by RNA-seq. Compare results to 12-month Relapse-Free Survival rate using statistical methods.	12 months
Number of DNA Mutations as Measured by Whole Transcriptome	Number of DNA mutations as measured by whole transcriptome. Compare results to 3-month Complete Response rate.	3 months
Number of DNA Mutations as Measured by Whole Exome	Number of DNA mutations as measured by whole exome. Compare results to 3-month Complete Response rate.	3 months
Number of DNA Mutations as Measured by Panel DNA Sequencing	Number of DNA mutations as measured by panel DNA sequencing. Compare results to 3-month Complete Response rate.	3 months
Type of DNA Mutations as Measured by Whole Transcriptome	Type of DNA mutations as measured by whole transcriptome. Compare results to 3-month Complete Response rate.	3 months
Type of DNA Mutations as Measured by Whole Exome	Type of DNA mutations as measured by whole exome. Compare results to 3-month Complete Response rate.	3 months
Type of DNA Mutations as Measured by Panel DNA Sequencing	Type of DNA mutations as measured by panel DNA sequencing. Compare results to 3-month Complete Response rate.	3 months
Number of DNA Mutations as Measured by Whole Transcriptome	Number of DNA mutations as measured by whole transcriptome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.	12 months
Number of DNA Mutations as Measured by Whole Exome	Number of DNA mutations as measured by whole exome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.	12 months
Number of DNA Mutations as Measured by Panel DNA Sequencing	Number of DNA mutations as measured by panel DNA sequencing. Compare results to 12-month Relapse Free Survival rate using statistical analysis.	12 months
Type of DNA Mutations as Measured by Whole Transcriptome	Type of DNA mutations as measured by whole transcriptome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.	12 months
Type of DNA Mutations as Measured by Whole Exome	Type of DNA mutations as measured by whole exome. Compare results to 12-month Relapse Free Survival rate using statistical analysis.	12 months
Type of DNA Mutations as Measured by Panel DNA Sequencing	Type of DNA mutations as measured by panel DNA sequencing. Compare results to 12-month Relapse Free Survival rate using statistical analysis.	12 months
Numbers of T-cell Subpopulations	Numbers of t-cell subpopulations utilizing immunohistochemical (IHC) staining and flow cytometry. Compare results to 3-month Complete Response rate using statistical analysis.	3 months
Ratio of T-cell Subpopulations	Ratio of t-cell subpopulations utilizing IHC staining and flow cytometry. Compare results to 3-month Complete Response rate using statistical analysis.	3 months
Numbers of T-cell Subpopulations	Numbers of t-cell subpopulations utilizing IHC staining and flow cytometry. Compare results to 12-month Relapse-Free Survival rate using statistical analysis.	12-months
Ratio of T-cell Subpopulations	Ratio of t-cell subpopulations utilizing IHC staining and flow cytometry. Compare results to 12-month Relapse-Free Survival rate using statistical analysis.	12-months

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Max Kates, MD, Johns Hopkins University

Publications and helpful links

Helpful Links

• Sidney Kimmel Comprehensive Cancer Center website

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): October 4, 2022
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 8, 2020
• First Posted (Actual): May 13, 2020

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: NMIBC
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Gemcitabine
• Other Study ID Numbers: J2020; IRB00241941 (Other Identifier: Johns Hopkins Institutional Review Boards)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes